NANOTECHNOLOGY HORIZONS

IN FOOD PROCESS ENGINEERING

Volume 3

Trends, Nanomaterials, and Food Delivery

Nanotechnology Horizons in Food Process Engineering, Set of 3 Vols

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Nanotechnology Horizons in Food Process Engineering, Vol 1:

Food Preservation, Food Packaging, and Sustainable Agriculture
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Nanotechnology Horizons in Food Process Engineering, Vol 3:

Trends, Nanomaterials, and Food Delivery
ISBN: 978-1-77491-098-6 (hbk)

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 Innovations in Agricultural and Biological Engineering

NANOTECHNOLOGY HORIZONS

IN FOOD PROCESS ENGINEERING

Volume 3

Trends, Nanomaterials, and Food Delivery

Edited by
Megh R. Goyal, PhD, PE

Santosh K. Mishra, PhD

Satish Kumar, PhD

First edition published 2023

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Library and Archives Canada Cataloguing in Publication

Title: Nanotechnology horizons in food process engineering / edited by Megh R. Goyal, PhD, PE, Santosh K. Mishra, PhD,
Satish Kumar, PhD.
Names: Goyal, Megh R., editor. | | Mishra, Santosh K., editor. | Kumar, Satish (Lecturer in food science and technology), editor.
Series: Innovations in agricultural and biological engineering.
Description: First edition. | Series statement: Innovations in agricultural and biological engineering | Includes bibliographical
references and indexes. | Contents: Volume 3. Trends, nanomaterials, and food delivery.
Identifiers: Canadiana (print) 20220408009 | Canadiana (ebook) 20220408033 | ISBN 9781774910641 (set) |
ISBN 9781774910993 (v. 3 ; softcover) | ISBN 9781774910986 (v. 3 ; hardcover) | ISBN 9781003305408 (v. 3 ; ebook)
Subjects: LCSH: Food—Biotechnology. | LCSH: Food industry and trade—Technological innovations. |
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ISBN: 978-1-77491-098-6 (hbk)

ISBN: 978-1-77491-099-3 (pbk)
ISBN: 978-1-00330-540-8 (ebk)
ABOUT THE BOOK SERIES:
INNOVATIONS IN AGRICULTURAL
AND BIOLOGICAL ENGINEERING

Under this book series, Apple Academic Press Inc. is publishing book
volumes over a span of 8–10 years in the specialty areas defined by the
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vi About the Book Series

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For more information on this series, readers may contact:
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OTHER BOOKS ON AGRICULTURAL
AND BIOLOGICAL ENGINEERING BY
APPLE ACADEMIC PRESS, INC.

Management of Drip/Trickle or Micro Irrigation

Megh R. Goyal, PhD, PE, Senior Editor-in-Chief
Evapotranspiration: Principles and Applications for Water Management
Megh R. Goyal, PhD, PE, and Eric W. Harmsen, Editors

Book Series: Research Advances in Sustainable Micro Irrigation

Senior Editor-in-Chief: Megh R. Goyal, PhD, PE
• Volume 1: Sustainable Micro Irrigation: Principles and Practices
• Volume 2: Sustainable Practices in Surface and Subsurface Micro
Irrigation
• Volume 3: Sustainable Micro Irrigation Management for Trees and
Vines
• Volume 4: Management, Performance, and Applications of Micro
Irrigation Systems
• Volume 5: Applications of Furrow and Micro Irrigation in Arid and
Semi-Arid Regions
• Volume 6: Best Management Practices for Drip Irrigated Crops
• Volume 7: Closed Circuit Micro Irrigation Design: Theory and
Applications
• Volume 8: Wastewater Management for Irrigation: Principles and
Practices
• Volume 9: Water and Fertigation Management in Micro Irrigation
• Volume 10: Innovation in Micro Irrigation Technology
Book Series: Innovations and Challenges in Micro Irrigation
Senior Editor-in-Chief: Megh R. Goyal, PhD, PE
• Engineering Interventions in Sustainable Trickle Irrigation: Water
Requirements, Uniformity, Fertigation, and Crop Performance
• Management Strategies for Water Use Efficiency and Micro Irrigated
Crops: Principles, Practices, and Performance
viii Other Books on Agricultural and Biological Engineering

• Micro Irrigation Engineering for Horticultural Crops: Policy Options,

Scheduling, and Design
• Micro Irrigation Management: Technological Advances and Their
Applications
• Micro Irrigation Scheduling and Practices
• Performance Evaluation of Micro Irrigation Management: Principles
and Practices
• Potential of Solar Energy and Emerging Technologies in Sustainable
Micro Irrigation
• Principles and Management of Clogging in Micro Irrigation
• Sustainable Micro Irrigation Design Systems for Agricultural Crops:
Methods and Practices
Book Series: Innovations in Agricultural and Biological Engineering
Senior Editor-in-Chief: Megh R. Goyal, PhD, PE
• Advanced Research Methods in Food Processing Technologies
• Advances in Food Process Engineering: Novel Processing,

Preservation and Decontamination of Foods

• Advances in Green and Sustainable Nanomaterials: Applications in

Energy, Biomedicine, Agriculture, and Environmental Science
• Advances in Sustainable Food Packaging Technology
• Analytical Methods for Milk and Milk Products, Volume 1:

Sampling Methods, Chemical and Compositional Analysis

• Analytical Methods for Milk and Milk Products, Volume 2:

Physicochemical Analysis of Concentrated, Coagulated and

Fermented Products

• Biological and Chemical Hazards in Food and Food Products:

Prevention, Practices, and Management

• Bioremediation and Phytoremediation Technologies in Sustainable

Soil Management, Volume 1: Fundamental Aspects and
Contaminated Sites
• Bioremediation and Phytoremediation Technologies in Sustainable
Soil Management, Volume 2: Microbial Approaches and Recent
Trends
• Bioremediation and Phytoremediation Technologies in Sustainable
Soil Management, Volume 3: Inventive Techniques, Research
Methods, and Case Studies
• Bioremediation and Phytoremediation Technologies in Sustainable
Soil Management, Volume 4: Degradation of Pesticides and
Polychlorinated Biphenyls
Other Books on Agricultural and Biological Engineering ix

• Dairy Engineering: Advanced Technologies and Their Applications

• Developing Technologies in Food Science: Status, Applications, and
Challenges
• Emerging Technologies in Agricultural Engineering
• Engineering Interventions in Agricultural Processing
• Engineering Interventions in Foods and Plants
• Engineering Practices for Agricultural Production and Water
Conservation: An Interdisciplinary Approach
• Engineering Practices for Management of Soil Salinity: Agricultural,
Physiological, and Adaptive Approaches
• Engineering Practices for Milk Products: Dairyceuticals, Novel
Technologies, and Quality
• Enzyme Inactivation in Food Processing: Technologies, Materials,
and Applications
• Field Practices for Wastewater Use in Agriculture: Future Trends and
Use of Biological Systems
• Flood Assessment: Modeling and Parameterization
• Food Engineering: Emerging Issues, Modeling, and Applications
• Food Process Engineering: Emerging Trends in Research and Their
Applications
• Food Processing and Preservation Technology: Advances, Methods,
and Applications
• Food Technology: Applied Research and Production Techniques
• Functional Dairy Ingredients and Nutraceuticals: Physicochemical,
Technological, and Therapeutic Aspects
• Handbook of Research on Food Processing and Preservation
Technologies: Volume 1: Nonthermal and Innovative Food
Processing Methods
• Handbook of Research on Food Processing and Preservation
Technologies, Volume 2: Nonthermal Food Preservation and Novel
Processing Strategies
• Handbook of Research on Food Processing and Preservation
Technologies, Volume 3: Computer-Aided Food Processing and
Quality Evaluation Techniques
• Handbook of Research on Food Processing and Preservation
Technologies, Volume 4: Design and Development of Specific
Foods, Packaging Systems, and Food Safety
• Handbook of Research on Food Processing and Preservation
Technologies, Volume 5: Emerging Techniques for Food Processing,
Quality, and Safety Assurance
x Other Books on Agricultural and Biological Engineering

• Modeling Methods and Practices in Soil and Water Engineering

• Nanotechnology and Nanomaterial Applications in Food, Health,
and Biomedical Sciences
• Nanotechnology Applications in Agricultural and Bioprocess
Engineering: Farm to Table
• Nanotechnology Applications in Dairy Science: Packaging,
Processing, and Preservation
• Nanotechnology Horizons in Food Process Engineering, Volume 1:
Food Preservation, Food Packaging, and Sustainable Agriculture
• Nanotechnology Horizons in Food Process Engineering, Volume 2:
Scope, Biomaterials, and Human Health
• Nanotechnology Horizons in Food Process Engineering, Volume 3:
Trends, Nanomaterials, and Food Delivery
• Novel and Alternative Methods in Food Processing:
Biotechnological, Physicochemical, and Mathematical Approaches
• Novel Dairy Processing Technologies: Techniques, Management,
and Energy Conservation
• Novel Processing Methods for Plant-Based Health Foods:
Extraction, Encapsulation and Health Benefits of Bioactive
Compounds
• Novel Strategies to Improve Shelf-Life and Quality of Foods:
Quality, Safety, and Health Aspects
• Phytochemicals and Medicinal Plants in Food Design: Strategies and
Technologies for Improved Healthcare
• Processing of Fruits and Vegetables: From Farm to Fork
• Processing Technologies for Milk and Milk Products: Methods,
Applications, and Energy Usage
• Quality Control in Fruit and Vegetable Processing: Methods and
Strategies
• Scientific and Technical Terms in Bioengineering and Biological
Engineering
• Soil and Water Engineering: Principles and Applications of
Modeling
• Soil Salinity Management in Agriculture: Technological Advances
and Applications
• State-of-the-Art Technologies in Food Science: Human Health,
Emerging Issues and Specialty Topics
• Sustainable Biological Systems for Agriculture: Emerging Issues in
Nanotechnology, Biofertilizers, Wastewater, and Farm Machines
Other Books on Agricultural and Biological Engineering xi

• Sustainable Nanomaterials for Biomedical Engineering: Impacts,

Challenges, and Future Prospects
• Sustainable Nanomaterials for Biosystems Engineering: Trends in
Renewable Energy, Environment, and Agriculture
• Technological Interventions in Dairy Science: Innovative
Approaches in Processing, Preservation, and Analysis of Milk
Products
• Technological Interventions in Management of Irrigated Agriculture
• Technological Interventions in the Processing of Fruits and
Vegetables
• Technological Processes for Marine Foods, From Water to Fork:
Bioactive Compounds, Industrial Applications, and Genomics
• The Chemistry of Milk and Milk Products: Physicochemical
Properties, Therapeutic Characteristics, and Processing Methods
ABOUT SENIOR-EDITOR-IN-CHIEF

Megh R. Goyal, PhD, PE

Retired Professor in Agricultural and Biomedical
Engineering, University of Puerto Rico,
Mayaguez Campus; Senior Acquisitions Editor,
Biomedical Engineering and Agricultural Science,
Apple Academic Press, Inc.

Megh R. Goyal, PhD, PE, is currently a Retired

Professor of Agricultural and Biomedical Engineering
in the General Engineering Department at the College of Engineering at
the University of Puerto Rico–Mayaguez Campus (UPRM); and Senior
Acquisitions Editor and Senior Technical Editor-in-Chief for Agricultural
and Biomedical Engineering for Apple Academic Press Inc.
During his long career, he has worked as a Soil Conservation Inspector;
Research Assistant at Haryana Agricultural University and Ohio State
University; Research Agricultural Engineer/Professor at the Department
of Agricultural Engineering of UPRM; and Professor of Agricultural and
Biomedical Engineering in the General Engineering Department of UPRM.
He spent a one-year sabbatical leave in 2002–2003 at the Biomedical Engi­
neering Department of Florida International University, Miami, USA.
Dr. Goyal was the first agricultural engineer to receive the professional
license in agricultural engineering from the College of Engineers and
Surveyors of Puerto Rico. In 2005, he was proclaimed the “Father of Irriga­
tion Engineering in Puerto Rico for the Twentieth Century” by the American
Society of Agricultural and Biological Engineers, Puerto Rico Section, for his
pioneering work on micro irrigation, evapotranspiration, agroclimatology,
and soil and water engineering.
During his professional career of 52 years, he has received many awards,
including Scientist of the Year, Membership Grand Prize for the American
Society of Agricultural Engineers Campaign, Felix Castro Rodriguez
Academic Excellence Award, Man of Drip Irrigation by the Mayor of
Municipalities of Mayaguez/Caguas/Ponce and Senate/Secretary of Agricul­
ture of ELA, Puerto Rico, and many others. He has been recognized as one of
the experts “who rendered meritorious service for the development of [the]
xiv About Senior-Editor-in-Chief

irrigation sector in India” by the Water Technology Centre of Tamil Nadu

Agricultural University in Coimbatore, India, and ASABE who bestowed on
him the 2018 Netafim Microirrigation Award.
Dr. Goyal has authored more than 200 journal articles and edited more
than 100 books. AAP has published many of his books, including Manage­
ment of Drip/Trickle or Micro Irrigation; Evapotranspiration: Principles and
Applications for Water Management; ten-volume set on Research Advances
in Sustainable Micro Irrigation. Dr. Goyal has also developed several book
series with AAP, including Innovations in Agricultural & Biological Engi­
neering (with over 60 titles in the series to date), Innovations and Challenges
in Micro Irrigation; and Innovations in Plant Science for Better Health: From
Soil to Fork.
Dr. Goyal received his BSc degree in Engineering from Punjab Agri­
cultural University, Ludhiana, India, and his MSc and PhD degrees from
the Ohio State University, Columbus, Ohio, USA. He also earned a Master
of Divinity degree from the Puerto Rico Evangelical Seminary, Hato Rey,
Puerto Rico, USA.
Readers may contact him at [email protected].
ABOUT THE EDITORS

Santosh Kumar Mishra, PhD

Assistant Professor, Department of Dairy Microbiology,
College of Dairy Science and Technology, Guru Angad
Dev Veterinary and Animal Sciences University,
Ludhiana, Punjab, India

Santosh Kumar Mishra, PhD, is working as an Assistant

Professor in Department of Dairy Microbiology, College
of Dairy Science and Technology, Guru Angad Dev
Veterinary and Animal Sciences University, Ludhiana,
Punjab, India. He is working in the area of functional
foods and dairy products incorporating live probiotics, technology of
functional lactic cultures for fermented and non-fermented dairy products.
He previously served the dairy industry as a Quality Assurance Executive
at Mother Dairy, New Delhi. In India, he has handled externally funded
projects granted by DST, MoFPI, and UGC as principal investigator or
co- principal investigator. He has received several awards for best papers
and posters/presentations. He is the recipient of junior and senior research
fellowship during his master’s and doctoral programs at the National Dairy
Research Institute, Karnal, Haryana. He is university gold medalist during
his graduation program and also received the best thesis award by his
university for his PhD research. Recently he has received an Award of Honor
at an international conference sponsored by the Partap College of Education,
Ludhiana, in association with the International Professionals Development
Association, UK. He is a member of various scientific societies, including
life member of SASNET-Fermented Foods, Anand, and member of Indian
Dairy Association, New Delhi.
Dr. Mishra has published several research, review, and popular articles in
national and international journals. He has also published five international
edited books, several book chapters, and teaching reviews in various training
programs. He has recently completed the young scientist project by DST,
Science for Equity Empowerment and Development (SEED)
xvi About the Editors

Department, Government of India, New Delhi, on Isolation and

characterization of novel oxalate degrading lactic acid bacteria for potential
probiotic management of kidney stone.
Dr. Mishra received his BTech degree in Dairy Technology from
Maharashtra Animal and Fisheries Sciences University, Nagpur, India; and
his MSc and PhD degrees from National Dairy Research Institute, Karnal,
Haryana, India.
Readers may contact him at: [email protected].

Satish Kumar, PhD

Assistant Professor (Food Science and Technology),
College of Horticulture and Forestry, Thunag-Mandi,
Dr. Y.S. Parmar University of Horticulture and Forestry,
Nauni-Solan – 173230, Himachal Pradesh, India

Satish Kumar, PhD, is an Assistant Professor (Food

Science and Technology) in the College of Horticulture
and Forestry at Dr. Y.S. Parmar University of Horticulture and Forestry
in Himachal Pradesh, India. He is currently working in the area of
characterization of edible nano-emulsions for reducing post-harvest losses
of fresh horticultural produce. He is also associated with the development
of novel animal food analogs (milk and meat analogs) and protocols
for utilization of waste generated from the agricultural and horticultural
processing industry by cradle-to-cradle regenerative conceptualization.
Dr. Kumar served at Lovely Professional University, Phagwara-Punjab,
India, as Assistant Professor (Food Technology and Nutrition). He has
successfully guided 19 MSc scholars of Food Technology and Nutrition. He
has participated in several national and international conferences, seminars,
workshops, training, symposiums, etc. He is serving as an editorial board
member for Archives of Food Science and Nutrition Research and Global
Journal of Food Science and Technology.
He has to his credit 52 research papers, 12 book chapters, five conference
papers and five abstracts. He has published papers in journals including
Trends in Food Science and Technology and Critical Reviews in Food
Science and Nutrition. His cumulative NAAS score is 290 and impact
factor is 150. He is serving as an external examiner for various Indian state
agricultural universities. He is also serving as editor and reviewer for several
peer-reviewed journals of international repute. He is the Joint Secretary in
About the Editors xvii

Functional Food Association of India (FFAI) [Registered under HP Societies

Registration Act, 2006]
Dr. Kumar holds a BSc (2011) in Horticulture, MSc (2013), and PhD
(2018) in Food Technology from Dr. Y. S. Parmar University of Horticulture
and Forestry Nauni-Solan (Himachal Pradesh), India. He has qualified
ICAR, ASRB-NET (2014), and holds two course diplomas on enhancing
soft skills and personality development (2018) and dairy and food process
and products technology (2019) from the Indian Institute of Technology,
Kanpur (Ministry of HRD, Government of India).
Readers may contact him at: [email protected]
CONTENTS

Contributors........................................................................................................... xxi

Abbreviations ........................................................................................................ xxv

Preface ............................................................................................................... xxxiii

Part I: Current Trends in Nanotechnology for Food Applications ....................1

1. Stability and Fate of Nanoparticles in Foods ...............................................3

Amisha Kushwaha, Gajendar Singh, and Manu Sharma

2. Nano-Biosensing for Detection of Food Contaminants .............................45

Mathivanan Sivaji, Muthuraman Yuvaraj, Eman Tawfik Hussien,

Thangaraj Thilagavathi, and Pachamuthu Ayyadurai

Part II: Innovative Technologies in Nanomaterials for

Food Applications..........................................................................................73

3. Nanotechnology Applications in Agriculture..............................................75

Pankaj Kumar, Karuna Dhiman, Ishani Shaunak, Geetika Gambhir,

Arun Kumar, and Dinesh K. Srivastava

4. Postharvest Physiology, Value Chain Advancement, and

Nanotechnology in Fresh-Cut Fruits and Vegetables ................................99

Neeru Dubey, Srishti Chitranshi, Shailendra K. Dwivedi, and Anshu Sharma

5. Role of Nanotechnology in Nutrient Delivery ..........................................133

Deepshikha Rawat, Vidisha Tomer, Sanskriti Pandey, and Seherpreet Kaur Flora

6. Implications of Nanotechnology in Food Packaging................................161

Anshu Sharma, Amisha Sharma, Marisha Baurai, Nancy Loria, Neeru Dubey,

and Vijay Yadav Tokala

7. Applications of Nanotechnology in the Dairy Industry...........................207

Samriti Guleria, Mukul Kumar, Vikas Bansal, and Ashwani Kumar

Part III: Nanotechnology to Improve Food Delivery Systems........................225

8. Antimicrobial Nanoparticles: Production, Mechanism

of Action, and Applications in the Food Sector ........................................227

Saurabh Sharma, Ajay Sharma, Shailja Sankhyan, Anil Kumar, and Anil K. Sharma
xx Contents

9. Nanoencapsulation of Bioactive Compounds ...........................................285

Neha Sharma, Mudasir Yaqoob, Prastuty Singh, Gurkirat Kaur,

and Poonam Aggarwal

10. Development of Nutraceuticals Using Nanotechnological Tools:

Current Scenario and Future Prospects ..................................................335

Eman Tawfik Hussien, Muthuraman Yuvaraj, Mathivanan Sivaji,

and Thangaraj Thilagavathi

11. Potential of Biofunctional Magnetic Nanoparticles in

Food Safety: Detection of Toxins and Foodborne Pathogens..................353

Sharad Raghuvanshi, Hina Khan, Vaishali Saroha, Jitendra Singh,

Ashish Kadam, and Dharm Dutt

Index......................................................................................................................401

CONTRIBUTORS

Poonam Aggarwal
Senior Vegetable Technologist, Department of Food Science and Technology,

Punjab Agricultural University, Ludhiana – 141004, Punjab, India,

Mobile: +91-9855055871, E-mail: [email protected]

Pachamuthu Ayyadurai
Assistant Professor, Agricultural College and Research Institute, Tamil Nadu Agricultural University,

Vazhavachanur – 606753, Tiruvannamalai, Tamil Nadu, India,

Mobile: +91-9994929198, E-mail: [email protected]

Vikas Bansal
Assistant Professor, Department of Food Technology, School of Engineering Technology,

Jaipur National University, Jagatpura – 302025, Jaipur, India,

Mobile: +91-9816922595, E-mail: [email protected]

Marisha Baurai
Horticulture-PHT, Amity Institute of Horticulture Studies and Research, Amity University,
Noida–201313, Uttar Pradesh, India, Mobile: +91-9871215870, E-mail: [email protected]
Srishti Chitranshi
PhD Research Scholar, Amity Institute of Horticulture Studies and Research, Amity University,

Noida – 201313, Uttar Pradesh, India, Mobile: +91-9717430467, E-mail: [email protected]

Karuna Dhiman
Assistant Professor, Department of Biotechnology, College of Horticulture and Forestry, Neri,
Hamirpur, Affiliated to Dr. Y.S. Parmar University of Horticulture and Forestry, Solan – 173230,
Himachal Pradesh, India, Mobile: +91-8219017872, E-mail: [email protected]

Neeru Dubey
Associate Professor, Horticulture, Amity International Center for Postharvest technology and Cold
Chain Management, Amity University, Noida – 201313, Uttar Pradesh, India,
Mobile: +91-9891078954, E-mail: [email protected]

Dharm Dutt
Professor, Department of Paper Technology, Indian Institute of Technology – Roorkee
(Saharanpur Campus), Saharanpur – 247001, Uttar Pradesh, India,
Mobile: +91-9897082949, E-mail: [email protected]

Shailendra K. Dwivedi
Assistant Professor, College of Horticulture, Madhya Pradesh, Raj Mata Viyayraje Scibndia,

Krishi Vishwavidyalaya, Mandsaur – 458002, Madhya Pradesh, India,

Mobile +91-8959025045, E-mail: [email protected]

Seherpreet Kaur Flora

MSc Student, Food Technology and Nutrition, School of Agriculture, Lovely Professional University,
Phagwara – 144411, Punjab, India, Mobile: +917225889840, E-mail: [email protected]

Geetika Gambhir
Research Fellow, ICAR – Indian Agricultural Research Institute (IARI), New Delhi, India,
Mobile: +91-9953316732, E-mail: [email protected]
xxii Contributors

Megh R. Goyal
Retired Faculty in Agricultural and Biomedical Engineering from College of Engineering at University
of Puerto Rico – Mayaguez Campus, and Senior Technical Editor-in-Chief in Agricultural and
Biomedical Engineering for Apple Academic Press Inc., PO Box 86, Rincon – PR – 006770086, USA,
E-mail: [email protected]

Samriti Guleria
PhD Research Scholar, Food Technology and Nutrition, School of Agriculture,

Lovely Professional University, Phagwara – 144411, Punjab, India,

Mobile: +91-9817087183, E-mail: [email protected]

Eman Tawfik Hussien

Lecturer of Genetics and Genetic Engineering, Faculty of Science, Helwan University, Egypt – 11795,
Mobile: +201-119383526, E-mail: [email protected]

Ashish Kadam
Research Scientist, Department of Paper Technology, Indian Institute of Technology – Roorkee
(Saharanpur Campus), Saharanpur – 247001, Uttar Pradesh, India,
Mobile: +91-9917180443, E-mail: [email protected]

Gurkirat Kaur
Assistant Professor, Department of Food Science and Technology, Punjab Agricultural University,
Ludhiana – 141004, Punjab, India, Mobile: +91-9501134768, E-mail: [email protected]

Hina Khan
PhD Research Scholar, Department of Paper Technology, Indian Institute of Technology – Roorkee
(Saharanpur Campus), Saharanpur – 247001, Uttar Pradesh, India,
Mobile: +91-8791519756, E-mail: [email protected]

Anil Kumar
Professor, Department of Microbiology, DAV University, Jalandhar, Punjab, India,
Mobile: +91-9805046114, E-mail: [email protected]

Arun Kumar
Senior Scientist, Biotechnology Division, CSIR-Institute of Himalayan Bioresource Technology,
Palampur – 176061, Himachal Pradesh, India, Mobile: +91-9418830880, E-mail: [email protected]

Ashwani Kumar
Assistant Professor, Food Technology and Nutrition, School of Agriculture,
Lovely Professional University, Phagwara – 144411, Punjab, India,
Mobile: +91-8146941884, E-mail: [email protected]

Mukul Kumar
Assistant Professor, Food Technology and Nutrition, School of Agriculture,
Lovely Professional University, Phagwara – 144411, Punjab, India,
Mobile: +91-8988227729, E-mail: [email protected]

Pankaj Kumar
Assistant Professor, Department of Biotechnology, College of Horticulture and Forestry, Neri,
Hamirpur, Affiliated to Dr. Y.S. Parmar University of Horticulture and Forestry, Solan – 173230,
Himachal Pradesh, India, Mobile: +91-8219034254, E-mail: [email protected]

Amisha Kushwaha
PhD Research Scholar, Central University of Gujarat (CUG), Sector-30, Gandhinagar – 382030,
Gujarat, India, Mobile: +91-7990026564, E-mail: [email protected]
Contributors xxiii

Nancy Loria
Department of Environmental Science, College of Forestry, Dr. Yashwant Singh Parmar University of
Horticulture and Forestry, Nauni – 173230, Solan, Himachal Pradesh, India,
Mobile: +1-801-915-6002, E-mail: [email protected]

Sanskriti Pandey
MSc Student, Food Technology and Nutrition, School of Agriculture, Lovely Professional University,
Phagwara – 144411, Punjab, India, Mobile: +91-9807187892, E-mail: [email protected]
Sharad Raghuvanshi
PhD Research Scholar, Department of Paper Technology, Indian Institute of Technology – Roorkee
(Saharanpur Campus), Saharanpur – 247001, Uttar Pradesh, India,
Mobile: +91-8218209492, E-mail: [email protected]

Deepshikha Rawat
MSc Student, Food Technology and Nutrition, School of Agriculture, Lovely Professional University,
Phagwara – 144411, Punjab, India, Mobile: +91-9760389148, E-mail: [email protected]
Shailja Sankhyan
Assistant Professor, Department of Biotechnology, Chandigarh University Gharuan, Mohali,
Punjab, India, Mobile: +91-9805167398, E-mail:[email protected]
Vaishali Saroha
PhD Research Scholar, Department of Paper Technology, Indian Institute of Technology – Roorkee
(Saharanpur Campus), Saharanpur – 247001, Uttar Pradesh, India,
Mobile: +91-7906111376, E-mail: [email protected]

Ajay Sharma
Assistant Professor, Department of Chemistry, Career Point University, Tikker-Kharwarian, Hamirpur,
Himachal Pradesh, India, Mobile: +91-9816259656, E-mail: [email protected]
Amisha Sharma
Horticulture-PHT, Amity Institute of Horticulture Studies and Research, Amity University,

Noida – 201313, Uttar Pradesh, India, Mobile: +91-9682540216, E-mail: [email protected]

Anil K. Sharma
Professor and Head, Department of Biotechnology, Maharishi Markandeshwar
(Deemed to be University) University, Mullana, Ambala, Haryana, India,
Mobile: +91-8059777758, E-mail: [email protected]

Anshu Sharma
Scientist, Department of Food Science and Technology, Dr. Y.S. Parmar University of
Horticulture and Forestry, Nauni – 17320, Solan, Himachal Pradesh, India,
Mobile: +91-8219884944, E-mail: [email protected]

Manu Sharma
Assistant Professor, School of School of Nano Sciences, Central University of Gujarat (CUG),

Sector-30, Gandhinagar – 382030, Gujarat, India,

Mobile: +91-7990026564, E-mail: [email protected]

Neha Sharma
PhD Research Scholar, Department of Food Science and Technology, Punjab Agricultural University,
Ludhiana – 141004, Punjab, India, Mobile: +91-9582923756, E-mail: [email protected]

Saurabh Sharma
PhD Research Scholar, Department of Chemistry, Career Point University, Tikker-Kharwarian, Hamirpur,
Himachal Pradesh, India, Mobile: +91-7018424290, E-mail: [email protected]
xxiv Contributors

Ishani Shaunak
PhD Research Scholar, Department of Biotechnology, College of Horticulture and Forestry, Neri,
Hamirpur, Affiliated to Dr. Y.S. Parmar University of Horticulture and Forestry, Solan – 173230,
Himachal Pradesh, India, Mobile: +91-8219716349, E-mail: [email protected]

Gajendar Singh
PhD Research Scholar, Central University of Gujarat (CUG), Sector-30, Gandhinagar – 382030,
Gujarat, India, Mobile: +91-9408663139, E-mail: [email protected]

Jitendra Singh
PhD Research Scholar, Department of Polymer and Process Engineering,

Indian Institute of Technology – Roorkee (Saharanpur Campus), Saharanpur – 247001,

Uttar Pradesh, India, Mobile: +91-8865941381, E-mail: [email protected]

Prastuty Singh
PhD Research Scholar, Department of Food Science and Technology, Punjab Agricultural University,
Ludhiana – 141004, Punjab, India, Mobile: +91-9536664313, E-mail: [email protected]

Mathivanan Sivaji
Teaching Assistant, Agricultural College and Research Institute, Vazhavachanur, Tiruvannamalai,
Tamil Nadu, India, Mobile: +91-8098193231, E-mail: [email protected]

Dinesh K. Srivastava
Retired Professor, Department of Biotechnology, College of Horticulture and Forestry at
Neri – Hamirpur, Affiliated to Dr. Y.S. Parmar University of Horticulture and Forestry, Solan – 173230,
Himachal Pradesh, India, Mobile: +91-7973155048, E-mail: [email protected]

Thangaraj Thilagavathi
Teaching Assistant, Food Science and Nutrition, Agricultural College and Research Institute,
Tamil Nadu Agricultural University, Vazhavachanur – 606753, Tiruvannamalai, Tamil Nadu, India,
Mobile: +91-9943520700, E-mail: [email protected]

Vijay Yadav Tokala

Assistant Professor, Horticulture, Amity Institute of Horticulture Studies and Research, Amity University,
Noida – 201313, Uttar Pradesh, India, Mobile: +91-9866473520, E-mail: [email protected]

Vidisha Tomer
Assistant Professor, VIT School of Agricultural Innovations and Advanced Learning,

Vellore Institute of Technology (VIT), Vellore – 632014, Tamil Nadu, India,

Mobile: +91-7011421664, E-mail: [email protected]

Mudasir Yaqoob
Assistant Professor, Department of Food Science and Nutrition, Lovely Professional University,
Phagwara – 144402, Punjab, India, Mobile: +91-9419015722, E-mail: [email protected]

Muthuraman Yuvaraj
Teaching Assistant, Department of Soil Science and Agricultural Chemistry, Agricultural College and
Research Institute, Tamil Nadu Agricultural University, Vazhavachanur – 606753, Tiruvannamalai,
Tamil Nadu, India, Mobile: +91-9994057361, E-mail: [email protected]
ABBREVIATIONS

µg microgram
Ab antibodies
AChE acetylcholinesterase
AFB1 aflatoxin B1
AF-B2 aflatoxin B2
AFM atomic force microscope
AF-M1 aflatoxin M1
AF-M1-HRP AF-M1 conjugated with horseradish peroxidase
AF-MNPs amine-functionalized MNPs
Ag silver
Ag2O silver oxide
AgNPs silver nanoparticles
ALT alanine aminotransferase
Amp-MNP ampicillin coated on magnetic nanoparticles
AMPs antimicrobial peptides
APEDA Agricultural and Processed Food Products Export
Development Authority
APTES 3-aminopropyl triethoxysilane
ARE antioxidant response element
AST antimicrobial susceptibility testing
ATP adenine triphosphate
AU analytical ultracentrifugation
Au gold
AuNPs/GNP gold nanoparticles
BPA bisphenol A
C2H4 ethane
CaCl2 calcium chloride
Caco-2 cancer coli-2
CaCO3 calcium carbonate
CCE carbon-ceramic electrodes
CCs coacervates
CD ICs cyclodextrin inclusion complexes
cDNA-UCNP complementary DNA conjugated with UCNP
CDs cyclodextrins
xxvi Abbreviations

CdSe cadmium selenide

CFU colony-forming unit
CITREM citric acid esters of monoglycerides
CLA conjugated linoleic acid
CLSI Clinical and Laboratory Standards Institute
Cm centimeter
CMC carboxymethylcellulose
CNT carbon nanotube
Co. Ltd. company limited
CO2 carbon dioxide
CT cholera toxin
CTAB cetyl trimethyl ammonium bromide
Cu copper
CuO copper oxide
CVD chemical vapor deposition
DAGs diacylglycerols
DATEM diacetyl tartaric acid esters of monoglycerides
DE dextrose equivalent
Dex-IONP dextran-coated iron oxide nanoparticles
DHA docosahexaenoic acid
DLLME dispersive liquid-liquid micro-extraction
DLS dynamic light scattering
DNA deoxyribonucleic acid
DON deoxynivalenol
DRS dual recognition strategy
DSP downstream processing
E. coli Escherichia coli
EC European Commission
EDC/NHS carbodiimide /N-hydroxy-succinimide
EDX energy dispersive X-ray
EIP emulsion inversion point
EIS electrochemical impedance spectroscopy
ELISA enzyme-linked immunosorbent assays
ENMs engineered nanomaterials
EPA eicosapentaenoic acid
ERK extracellular regulated kinase
EUCAST European Committee on Antimicrobial Susceptibility
Testing
EVOH ethylene-vinyl alcohol
Abbreviations xxvii

FAO Food and Agriculture Organization

FDA Food and Drug Administration
FDI Foreign Direct Investment
Fe3O4-PDA polydopamine coated MNPs
FeO3 iron oxide
FePt iron-platinum
FOS fructo-oligosaccharides
FSMA Food Safety Modernization Act
FSSAI Food Safety and Standards Authority of India
GA gum Arabic
GALT gut-associated lymphoid tissue
GC gas chromatography
GCE glass carbon electrode
GC-MS gas chromatography coupled with mass spectrometry
GDP gross domestic product
GFL ganglioside functionalized liposome
GG-NCC gum nano-crystalline cellulose
GIT gastrointestinal tract
GM genetically modified
GM1 ganglioside monosialic acid 1
GPa gigapascal
GRAS generally recognized as safe
H2O2 hydrogen peroxide
HA hyaluronic acid
HDPE high density polyethylene
HLB hydrophile-lipophile balance
HOCs halogenated organic contaminants
HPLC high performance liquid chromatography
HRP horseradish peroxidase
HR-TEM high resonance transmittance microscopy
HT-29 human colon carcinoma cell line
IACs immunoaffinity column
IARC International Agency for Research on Cancer
ICP-MS inductively coupled plasma mass spectrometry
IgG immunoglobulin G
IL interleukin
ILN ionic liquid nanocomposites
IMS immunomagnetic separation
IPP isostatic propylene
xxviii Abbreviations

ISO International Standards Organization

JECFA Joint FAO and WHO Expert Committee on Food
Additives
kGy kilo grays
LC/LC-MS liquid chromatography or coupled with tandem mass
spectrometry
LDPE low-density polyethene
LDS low-density solvent
LFA lateral flow assay
LoD limit of detection
LSPR localized surface plasmon resonance
MAB/Mac-Ab monoclonal antibodies
MAP modified atmospheric packaging
MAPK mitogen-activated protein kinase
mbar millibar
M-CLEIA MNPs-based chemiluminescent enzyme immunoassay
M-ELISA MNPs-based ELISA
MFA microfrilliar angle
mg/kg milligram per kilogram
MG-NH magneto-gold nanohybrid
MG-NH–mAb MG-GH and monoclonal antibody conjugate
MgO magnesium oxide
MHA Mueller Hinton agar
MHB Mueller Hinton Broth
MIC minimum inhibitory concentration
MIP molecularly imprinted polymer
MMT montmorillonite
MNPs magnetic nanoparticles
MP microparticle
MRSA methicillin-resistant S. aureus
MTT montmorillonite
MWCNT multi-wall carbon nanotubes
NaOCl sodium hypochlorite
NC nanoclay
NLCs nano-structure lipid carriers
NM nanomaterial
nm nanometer
NM nitrocellulose membrane
NMR nuclear magnetic resonance
Abbreviations xxix

NPEFP nanoparticles enabled-food packing

NPs nanoparticles
Nrf2 nuclear erythroid 2-related factor 2
n-SiO2 nano silicon dioxide
NSLc nanostructure lipid carriers
NTF nanotechnology task force
n-TiN nano titanium nitride
n-TiO2 nano titanium dioxide
n-ZnO nano zinc oxide
O/W oil in water
O2 oxygen
OA-AuNPs oleylamine-coated AuNPs
OC-IONPs oleic acid-coated iron oxide nanoparticles
OMMT organophilic montmorillonite
OPP oxidative pentose phosphate
OSA-MS octenyl succinic anhydride-modified starch
OTA ochratoxin A
OTA-BSA ochratoxins A conjugated bovine serum albumin
OTs ochratoxins
PA phosphatidic acid
PA6 polyamide 6
PAB polyclonal antibody
PAL phenylalanine ammonia-lyase
PBST phosphate buffer saline with tween-20
PC phosphatidylcholine
PCBs polychlorinated biphenyls
PCR polymerase chain reaction
PCS photon correlation spectroscopy
PDA polydopamine
PDI polydispersity index
PE phosphotidyl ethanolamine
PEB piezoelectric biosensor
PEDT poly (3,4-ethylene dioxy thiophene)
PEG polyethylene glycol
PET polyethene terephthalate
PI phosphatidylinositol
PIC phase inversion composition
PIT phase inversion temperature
PLL poly-L-lysine
xxx Abbreviations

PLW physiological weight loss

PNCs polyethylene terephthalate
POD per-oxidase
POE polyoxyethylenated
PP polypropylene
ppb parts per billion
ppm parts per million
PPO poly-phenol-oxidase
PS polystyrene
PTWI provisional tolerable weekly intake
PVC polyvinyl chloride
PVP polyvinyl propylene
QC quality control
QCM quartz crystal microbalance
QD quantum dots
q-PCR quantitative real-time PCR
QUAT quaternary ammonium salt
RFID radio-frequency identification
RNA ribonucleic acid
ROS reactive oxygen species
RT-qPCR reverse transcriptase – quantitative polymerase chain
reaction
scCO2 supercritical carbon dioxide
SDF soluble dietary fiber
SDS sodium dodecyl sulfate
SE staphylococcal enterotoxins
SEA staphylococcus enterotoxin A
SEM scanning electron microscopy
SERS surface-enhanced Raman spectroscopy
Si silicon
SiO2 silicon oxide
SLN solid lipid nanoparticle
SLS sodium lauryl sulfate
SMP starch magnetic nanoparticles
SNC silicon-nitride cantilever
SNP silicon nanoparticles
SOR surfactant oil ratio
SPCEs screen-printed carbon electrodes
SPE solid-phase extraction
Abbreviations xxxi

SPI soy protein isolate

SPIONs superparamagnetic iron oxide nanoparticles
SPR surface plasmon resonance
SQUID superconducting quantum interference device
ss DNA single-stranded DNA
Strep-HRP streptavidin-horseradish peroxidase
Strep-MNP streptavidin-coated MNPs
SWNTs single-walled carbon nanotubes
TAGs triacylglycerols
TB targeted bioavailability
TCA tricarboxylic acid
TEM transmission electron microscopy
TEOS tetraethyl orthosilicate
Ti titanium
TiN titanium nitride
TiNPs titanium nanoparticles
TiO2 titanium dioxide
TLC thin-layer chromatography
TM trademark
TMB 3,3′,5,5′-tetramethylbenzidine
TNT tuberculosis necrotizing toxin
TPa tera pascal
TSST toxic shock syndrome toxin
TTIs time-temperature indicators
UCNP lanthanide-doped upconversion nanoparticles
USA United States of America
USDA U.S. Department of Agriculture
USEPA United States Environmental Protection Agency
USFDA United States Food and Drug Administration
UV ultraviolet
UV-Vis ultraviolet visible
WHO World Health Organization
WPC whey protein concentrate
wpd Wilkinson power divider
WPI whey protein isolate
WSSV white spot syndrome virus
XPS X-ray photoelectron spectroscopy
XRD X-ray diffraction pattern
ZEN zearalenone
xxxii Abbreviations

ZEN-BSA zearalenone-bovine serum albumin

ZnO zinc oxide
ZnS zinc sulfide
ZrO2 zirconium oxide
PREFACE

Food processing and preservation has been recognized as the sunrise sector
that is expected to come up in a big way in the years to come. In recent
years, various governments around the globe have focused on the reduc­
tion of the postharvest losses and production of high value functional food
products through effective and efficient value addition. Such products are
not only expected to fulfill the nutritional desires of the population but also
to exert the functional benefits to the consumers, which is the demand of
today’s millennium. The food industry, on one hand, provides diversified
food products to satisfy the palate from various raw material, and on the
other hand, also generates huge employment in rural and urban areas. There
has been a continuously increasing concern about the healthy well-being
of the general masses, resulting in the continuous innovations in the novel
food products in various sectors of food processing. Modern food preserva­
tion methods have evolved from the traditional technologies like heating,
cooling, drying, refrigeration, concentration, freezing, etc., which have been
reported to deteriorate the food quality by affecting the nutritional status,
texture, sensory attributes and the shelf life of the products. Keeping in view
various concerns related to the traditional food processing and preservation
methods, several novel food processing and preservation technologies have
been proposed to improve the quality, safety, and delivery of various food
components to the ultimate consumers.
Nanotechnology Horizons in Food Process Engineering: Volume 3:
Trends, Nanomaterials, and Food Delivery is a collection of various applica­
tions of the nanomaterials in the food industry for improving the food quality
with the highest level of functionality without compromising the safety of
the food products. The volume not only serves academicians but should also
be of great interest to researchers and those in the food processing industries
because it covers the most recent trends and expected growth of the nanosci­
ences in food process engineering. In the 21st century, the food processing
industry has moved one step further from the concept of minimal food
processing and the non-thermal techniques for novel food product develop­
ment and the products of nanomaterial incorporated food have started to
come up in the market. The literature on nanoscience and its applications in
the food industry reveals that it is one of the most researched areas in the last
xxxiv Preface

decade most of the work being dedicated to novel food product development
with improved delivery of bioactive compounds, management of the quality
and shelf life of the fresh produce, and controlled delivery of the nutrients in
the food and body.
Applications of nanotechnology in the food industry are vast and continu­
ously touching new horizons to change the perspective of the food. The most
recent applications and innovations of the nanoscience in the food industry
primarily targets the functional food compounds, their encapsulation for the
effective and safe delivery to the consumers. The book has been compiled in
three volumes, all dealing with the basic concepts of the nanotechnological
tools and their potential food applications to serve as a reference for the
researchers, students, scholars, industries, universities, and research centers.
Each chapter of the book has been designed to cover the foremost principles
and processes in the fabrication of the nanomaterials, keeping in view the
technological aspects for the potential improvement in the delivery of the
target functional bioactive compounds, stabilization, and unrestricted distri­
bution of the food with the highest level of functionality and acceptability
among consumers.
This book has been divided into three sections containing various
chapters:
• Part I: The first section of the volume attempts to explore and convey
the key concepts of nanotechnology, discussing thoroughly how the
nanostructures are fabricated and used in the food industry for various
purposes. Various processes and methods encompassing the tools and
principles of nanotechnology have been discussed thoroughly. This
section of the book focuses on the potential improvement of the crops
and food products utilizing various novel nanoparticles.
• Part II: The second section of the book has been devoted to the inno­
vative technologies in nanomaterials for food applications, and in this
section thorough discussion on the applications of nanotechnology
for ensuring higher production, technological aspects, and production
of novel functional food products has been covered. The chapters in
this section encompass the latest information and recent trends in the
areas of nutrient delivery, post-harvest management and food pack­
aging innovations by active involvement of the nanotechnological
tools. Each chapter has been supported with the most recent research
trends well illustrated with the help of tabulated data and figures.
• Part III: The third section of the book has been devoted to nanotech­
nology to improve food delivery systems. In this part of the book,
Preface xxxv

attempts has been done for the validation of the use of nanoparticles
in various food applications keeping in view the international obli­
gations. Chapters in this section have thorough discussions on the
interaction of the nanoparticles with the food and body, their safety
aspects, bio-transformation in light of the regulations imposed by
various organizations. Some of the chapters also discuss the role of
the nanosciences in detection of the food contaminates. In general,
this section shall provide a comprehensive summary of the develop­
ments made in the area of food safety, especially in the foods carrying
the nanomaterial to accomplish the betterment of mankind.
The book is output of researchers and academics around the globe who
positively responded to the call and with their passion for science provided
the soul to this compendium. We would like to thank all the contributors
who indeed devoted their valuable time for this brainstorming activity, and
we also feel indebted to all the contributors for sharing their vision with the
highest level of dedication and enthusiasm to complete this draft.
We also extend our sincere thanks to the editorial office of Apple
Academic Press, Inc. for their immense facilitation and suggestions right
through this assignment, alongside the AAP Production Staff for typesetting
the whole manuscript for bringing out this quality production. We hereby
appeal our readers their productive suggestions that may form the basis for
improving the future editions.
We take this opportunity to thank: (i) our families for their continuous
support and motivation with the showers of blessings in counteracting every
obstacle coming in the way during this assignment; (ii) The entire research
community to set in the highest standards for the budding scientists, their
continuous encouragement and endless scientific support as and when
required; (iii) At last but not the least our institutes: College of Engineering
– University of Puerto Rico; College of Dairy Science and Technology,
Guru Angad Dev Veterinary and Animal Sciences University (GADVASU),
Ludhiana, and Dr. Yashwant Singh Parmar University of Horticulture and
Forestry, Nauni HP for their support during the compilation of this book.
—Editors
 PART I

CURRENT TRENDS IN

NANOTECHNOLOGY FOR

FOOD APPLICATIONS

CHAPTER 1

STABILITY AND FATE OF

NANOPARTICLES IN FOODS
AMISHA KUSHWAHA, GAJENDAR SINGH, and MANU SHARMA

ABSTRACT

Nanoparticles are developed in the food through a natural process that are
self-originated, by routine processing or are intentionally fabricated and
added in the food for special functions. The risk of nanoparticles is caused
in food through processing or contamination. Nanomaterials are increasingly
becoming important due to their wide spectrum application and have become
the point of attention across the health care organizations. Nanotechnology
is the latest innovative and emerging technology for food manufacturers to
apply tactics for the development of novel food products through triple ‘P’
that is production, protection, and procurement in foods. Food nanotech­
nology although involve triple ‘P’ triumph in the food world but potent
toxicity of nanomaterials cannot be ignored. Certain nanoparticles can be
hitched to the body through tuned food where nanoparticles are applied for
textural, spectacular, rheological improvements. Some of the most commer­
cial applications of the nanomaterials in the food are for improvement of
the qualitative attributes as coloring, drug-releasing, flavoring, preserving,
and downstream processing (DSP) elements. In recent years, great attention
is attracted in the field of nanomaterials and their food applications espe­
cially the form they are incorporated in the food, their fate and pathways
by which they interact with the organs of gastrointestinal tract (GIT) and
the immune system. In this chapter, much emphasis has been laid on the
toxicity mechanisms of the additive nanomaterials, the age groups which
are most affected and potential preventive measures which can be adopted

Nanotechnology Horizons in Food Process Engineering, Volume 3. Megh R. Goyal, PhD, PE,
Santosh K. Mishra, PhD, & Satish Kumar, PhD (Eds.)
© 2023 Apple Academic Press, Inc. Co-published with CRC Press (Taylor & Francis)
4 Nanotechnology Horizons in Food Process Engineering, Volume 3

to prevent severe damage. The engineered nanomaterials (ENMs) dubiously

have both contradictory toxicity and beneficial effects. There is an urgent
need for the research and systematic studies on the stability and fate of the
nanomaterials to fill the knowledge gap and increase the applicability of
these novel materials in the food.

1.1 INTRODUCTION

Food nanoscience and technology research area is indulged in the formation

of nanomaterials, its characterization, and applied applications for improve­
ment of food quality. Nanomaterials are considered to be in the scale of
nanometer (nm) which ranges 1–100 nm with some exceptions. Controlling
the properties of materials at the structural level and obtaining originating
characteristic property in the scale of nano range could provide dynamic
properties to the materials that are beneficial in the convinced commercial
applications. Industries related to various segments of food processing tech­
nology utilizes nanomaterials for edible materials and with other fixtures
related to the final food product in downstream processing (DSP). From the
business point of view, DSP is more money-making than innovating and
manufacturing food. DSP is an innovative food processing technology that
involves quality control in respect to microbial and quantity testing and
involves the ingredient in appropriate integration, sensing, and sterilization
of container in which the processed food is packed for long travel sustain-
ability, enhancing shelf life, freshness, durability in breaking and rupturing.
Nanoparticles (NPs) specifically designed and incorporated into food prod­
ucts for better and improved rheological or flow and optical properties to
attract the customer concentration.
Originally, via natural processes, NPs are present in some of the edible
products, certain organelles of plant and animal cells. NPs may also be
created in the foods due to routine methods of cooking food in the kitchen
like mixing, grinding, homogenizing, frying, steaming or in the barbeques.
These conditioned properties are not intentionally incorporated in the food
but are generated consequently through processing acts. In accordance with
desired applications of food, NPs can also be engineered at the nanoscale
level to enhance the property of foods and are considered as engineered nano­
materials (ENMs). Thus, the food NPs can come under the two categories
primary as natural processed and secondary as ENMs. ENMs are intention­
ally added to the food through NPs delivery system, and it may inaccurately
Stability and Fate of Nanoparticles in Foods 5

be found in the food from the packaging materials used for food packaging
from which it may come into the food. ENMs can be described as those
NPs which are designed in esteem of their size, shape, composition, and
interfacial properties to succeed with desired effects of the active particles.
ENMs are employed in delivery system to cushion the nutrition and attract
values of foods, preservatives, color, aromatics, and are also used to alter the
topographical and spectacular validity of foods.
In broad range variety of the nano-size scale materials are being devel­
oped that proposes the plenty of potent application in the plethora to vision
the medical utilization of the food beyond its nutrition. In the medical
field, in place of many unresolved cases, ENMs is holding the promise to
include the use of targeted and managed drug release for many diseases and
in contrast, could be helpful for the imaging of live body [95]. The strong
interest in the engineering of these NPs for biomedical purposes attracted the
great interest of researchers to investigate in due respect the consequences
and probes associated with nanomaterials in the human body. Resultantly,
this attention of interest is augmenting the number of relevant studies on
“nanotoxicology” because it is directly related to human health. Moreover,
potentially NPs may cause either chronic or acute toxicity and thus their
biotransformation becomes important.
The emergence of toxicity of nanoparticles is depends evaluation of the
existing and generation new scientific data that allows conclusions to be
drawn on the safety of the NPs. Day by day, new combinations of NPs are
formulating which need to be tested properly and comprehended towards the
nanotoxicity. But the study of advanced NPs interaction with live cells for
toxicological studies is hindered via so many properties [19]. These factors
encompass several parameters like different size of same molecular compo­
sition, same size but different molecular composition, change in shapes and
different in surface coating as well as interaction of different types of cells
like variations in incubation times and NP concentration, etc.
The optimization of interaction of various nanoparticles for toxicity is
due to the lack of proper methods of testing and complications of undesired
interactions of the NPs with the cellular culture. There is an urgent need to
develop methods to study the nanomaterial nature in the complicated cellular
atmosphere, requirement for the improved presence of investigative tools to
illustrate nanostructured material properties and accuracy, and to study the
more appropriate and complex models for toxicity and lack of adequately
mimicry of in vivo environment.
6 Nanotechnology Horizons in Food Process Engineering, Volume 3

Nanoparticles are synthesized in laboratory under controlled environ­

ment of media in monitoring of dissolution and aggregation of nanoparticle
synthesis. Contrariwise, it is found that in nature the fate of NPs can vary in
according to their existence in natural environment, terrestrial, and aquatic
conditions and broadly depends on the media in which it is present [58].
These natural milieu of interaction of nanoparticles synthesis shows certain
challenges that the obtained nanoparticles can be considered characteristi­
cally in µg/L or µg/Kg. Further, more studies are required in the angle of
focusing for the characterization of these nanomaterials in hope to get more
resolved data, in sense of other than pure elemental composition more other
contaminants presence could change the association of agglomeration that
could affects the toxicity level in prepared NPs bearing food [28].
Many tools and techniques are obtainable to characterize nanomaterials
in powdered or colloidal state, and with this, there should be good and
suitable research methodology required crucially to assist the studies at the
subcellular level in the time function. When NPs come in close proximity
and interact with cells, they are introduced to many local vagaries of cells
in response to different biomolecular substances with concentration, ionic
strength, and change in pH [50]. These versatile vagaries properties of cell
interaction with NPs may influence their behavior. Therefore, the prescribed
technology available for the study of the behavior of NPs in the subcellular
level may be the center for the attraction for research. This concern validated
the local subcellular part and their NPs interaction peculiarly in chemical and
colloidal states with bio-functional stability which may results in the degra­
dation of NPs or may result in the toxic effects with loss of NP functioning
and properties [49]. When the ENPs are forced to deliver the desired effect
in cell cytosol, it employees the cytotoxicity despite endocytosed. Therefore,
it is important to examine the Nanomaterials on large basis to overcome the
future risk in cell endosome which could be the main cause of NP-mediated
toxicity. Latest food testing methods are focused on pesticide detection [42]
and change in brain regulation neurotransmitter [69].
On the other hand, inorganic nanomaterials of zero-valent form of metal
and metalloid like silver, gold, selenium, etc., oxide form of iron, titanium,
silicon, and zinc and metal molybdates have been studied for toxic ions as
well as biomolecules monitoring [70]. The present chapter aims to provide
the information and clear vision of complications associated with increased
toxicity and benefits of different forms of nanoparticles like organic nano­
materials of protein, lipids emulsions, carbohydrates, and vitamins in food.
This chapter focuses on properties, potential stability, and fate of NPs for
potential safety after ingestion.
Stability and Fate of Nanoparticles in Foods 7

1.2 DIMENSIONS OF NANOPARTICLES

On the basis of the texture of nanoparticles nanomaterial can be classified in

four dimensions of zero, one, two, three, and four dimensions (0D, 1D, 2D,
3D, and 4D) as shown in Figure 1.1.

FIGURE 1.1 Dimensions of nanoparticles: Zero dimension to four dimensions.

Dimensions of NPs influences the gastrointestinal tract (GIT) while,

the toxicity events inside are affected by different mechanisms. Smaller
nanoparticles obviously pass faster than larger ones in GIT and hence, they
dissolve and digest sooner comparatively within similar molecular compo­
sition [43]. The presence of chemical components in GIT like digestive
enzymes, phospholipids, bile salts, and mineral ions also has an impact on
engulfed nanomaterials. In intestine when small nanomaterials are in close
proximity of mucus layer that passes in through the pore size of mucus layer
biopolymer network. Now, beneath the mucus layer at the intestinal epithe­
lium cell, tight junction are present for Nanomaterials transport and they can
pass through either active or passive transport mechanism that again depends
on the size of the nanoparticles.
Size of nanoparticle shows the great effect on GIT in sense of degree of
toxicity. Smaller size NPs are readily dissolved and digested to pool in the
walls of the intestine than the larger nanoparticles with similar molecular or
elemental composition.

1.3 MAXIMUM POSSIBLE OUTCOMES OF NANOPARTICLES

Nanomaterial can be existing in environment either naturally or nanoma­

terial are engineered for the maintenance and improvement of the of food
that attract the attention toward food and induces the taste buds of tongue,
increase shelf life of food and enhances the nutritive value mostly in pharma
8 Nanotechnology Horizons in Food Process Engineering, Volume 3

food. Therefore, food nanoparticles can be classified as natural food nanopar­

ticles or manmade that are anthropogenic nanoparticles in food shown in
Figure 1.2. Mostly nanoparticles are organic, inorganic or a mixture of both.
However, the maximum possible outcomes of nanoparticles can be classified
to circumvent of natural, anthropogenic, organic, and inorganic nanoparticles
are shown in Figure 1.2.

FIGURE 1.2 Possible outcomes of pure and combined different types of nanoparticles.

1.3.1 ORGANIC NATURAL VERSUS ANTHROPOGENIC

NANOPARTICLES IN FOODS

The natural environment itself has the property to invent the nano range
materials by following the phenomenon of mustering that is bottom-up
synthesis and breaking of bulk material into small particles that is top-down
synthesis. Naturally, the food having nanoparticles has been consumed since
ancient times, and no noticeable toxicity has been observed. In brief, dairy
products have most active casein micelle nanomaterials. The particle size of
Stability and Fate of Nanoparticles in Foods 9

dairy product casein micelle ranges from 100 to 200 nm and comes under
the structural model of coat core, which is having tough sphere with protein
with calcium phosphate for stability coated over hairy κ-casein. These nano
range aggregations of micelle are nature engineered capsules helpful for the
transfer of micronutrients and a few examples are shown in Figure 1.3.

FIGURE 1.3 Examples of different types of organic and inorganic or natural or anthropogenic
nanoparticles.

1.3.1.1 PROTEINACEOUS NPS

Any nanoparticles are said to be its identity as nano due to the clustering of
few atoms of molecules which depends upon their stability. Likewise few
molecules of casein are stabilized in the small gatherings in the presence
of calcium phosphate ion to form casein micelles. Formed Casein nano
micelles are the most common protein NPs mostly could be observed in
dairy products and milk of bovines. These types of nano micelles from past
centuries to till date has been consumed by the humans and with a little
concern of potent of toxicity. Casein nano micelles arouses their synthesis in
the milk and nurture the infants by fulfilling the requirement of protein and
minerals in the living body. Therefore, researchers and engineers are deeply
10 Nanotechnology Horizons in Food Process Engineering, Volume 3

involved in developing the other interesting organic nanomaterials as the

food and nutrients or supplements additive [66].
Mostly, organic nanomaterials like protein NPs are utilized as the carrier
for the delivery system in the form of capsules as the envelop to protect
and target the bioactive materials of supplements, flavors, food coloring
and drugs [14]. Physical interactions involved in the formation of protein
nanomaterials by the aggregation of molecules comes under the consider­
ation of strong bonding and weak interactions. Strong bond of electrostatic
or covalent like disulfide in the presence of sulfide and weak interaction
like hydrogen bond, Van der Waals, hydrophobic interactions may result in
formation of the nanoparticles in the food. During synthesis of Protein NPs
the strong bonds and weak interaction plays the major role and can be tuned
accordingly to alter the NPs by varying the synthesis solution milieu like the
solvent quality, pH, temperature ionic strength, precursor type and reaction
condition, etc.
The fate of tuned or engineered protein nanoparticles in GIT depends
upon the property of the bonds, surface, texture, and size. Its particles are in
various sizes (100–200 nm) and the examples are gliadin, soy, casein, whey,
and many. Mostly, these particles are spherical in shape but fibrous shape
has also been observed. They possess the surface electrical property which
changes from negative to positive, or it can also become neutral, depending
upon the surrounding pH with its own isoelectric point. Sometimes excess
of protein nanomaterials digestion in GIT produces toxins like allergens and
uric acid create soreness or joint pain, swelling, and pain in the big toe,
ankle, or knee.
Non-metabolized protein nanomaterials are absorbed through the mucus
layer and interact with gut microbiota to give unpredictable effect. Better
bioavailability of protein nanomaterials shows good effect on human health
due bioactivity of incorporated nutraceuticals, drugs, or supplements.

1.3.1.2 LIPID OR EMULSION-BASED NANOPARTICLES

Lipids in the form of nanomaterials are present in widespread range of food

materials and considered their integrity in the form of NPs. Lipid or oil
nanomaterials-based beverage in the form of emulsion droplets are present
in fruit juices, most dairy materials, fortified water and soft drinks. A good
volume of lipid droplets in such food materials are of nanoscale measure­
ments with a size of <100 nm. Lipid encapsulated nanodroplets and particles,
Stability and Fate of Nanoparticles in Foods 11

preserve, and deliver bio-active materials like flavors, food colors, supple­
ments, antioxidants, and nutraceuticals to their targeted areas. The major
advantages of these NPs is their utilization for increasing the bioavailability
and functional performance. The optical transparent design is anticipated in
the beverages industry for the clear vision to increase the corporal firmness
and to enhance the stability against aggregation and gravitational separation.
Array of lipid nanomaterials of surfactant micelles sizes varies from
within nanometer for example solid type lipid NPs or liquid type oil emul­
sion droplets. Electrical property of lipid NPs depends upon the molecular
construction of the nano aggregates. Edible lipidic NPs are composed of
polar or neutral, polar lipid NPs molecules would be in the form of surfac­
tant, free fatty acid, phospholipid type and neutral molecules would be
hydrocarbons, monoacylglycerols, terrapins, TAGs (triacylglycerols), and
(diacylglycerols) DAGs [22]. The fate of liability of lipidic nanoparticles in
GIT rides on the enzymatic action and hydrolysis through lipases and phos­
pholipases, which attack upon the hydrolysable ester bond to release free
fatty acids and monoacylglycerols. Free fatty acids and monoacylglycerols
are then associated and incorporate within each other and become mixed
micelles, ready form to be absorbed by the GIT surface epithelium cells [5,
98]. These lipidic nanomaterials are recognized for their potential toxicity
and are generally absorbed and accumulated within the intestine and some
other organs. While, these type of nanomaterials increases the bioavailability
of bioactive hydrophobic materials which may clues to be the further some
unforeseen undesirable effects [97].
Some lipidic NPs comes in the category of not to be digested by the
gastric enzymatic action and can be absorbed as such in GIT. Non-gastric
digestible lipidic nanostructures come under the group of oil phase materials
such as hydrocarbons which are used in flavors, essential oils, mineral oils
and terpenes, etc. Nanomaterial oil droplets are covered in the interfacial
layer that is helpful in inhibition of action of digestive enzyme to hydrolyze
[43, 79]. Moreover, no reports are available on the fate of non-digestible
nano lipidic particles after absorption and potent toxicity on human beings.

1.3.1.3 CARBOHYDRATE POLYMERIC NPS

Like lipidic nanoparticles, carbohydrate NPs can be lacerate as digestible

or non-digestible in the GIT. Components of carbohydrate nanomaterials
are built of polysaccharides xanthan, starch, pectin, cellulose, alginate,
12 Nanotechnology Horizons in Food Process Engineering, Volume 3

carrageenan, etc., through which NPs can be synthesized by using top-down

approach because polysaccharides are the large polymer structures and
sometimes branched which can be used to create the large accumulates.
Thus, the breaking down of the large accumulates forms the granular or
fibrillar texture of carbohydrate is essential for the fabrication of the NPs
[62]. In by-pass, carbohydrate nanoparticles can be engineered bottom-up
approach through aggregation of small molecules of polysaccharide by using
varying parameters of temperature, pressure or reducing agents, additive
supportive surfactant or minerals ion, etc. Different approaches of synthesis
can acquire different textures may be spherical or non-spherical, inspired by
the phenomenon of digestion in GIT [51].
GIT enzyme amylase can hydrolyze starch into oligosaccharides to
glucose. Alpha form of amylase is released in mouth from salivary gland
is said to be ptyalin and in small intestine it is released and produced by
pancreas. Some type of starch molecule having different structural organiza­
tion that acquire property of resistant to hydrolysis through digestive enzyme
amylase [26]. Other than starch many other non-digestible polysaccharides
are utilized for the formation of carbohydrate NPs collectively known as
dietary fibers.
Dietary fibers cannot be hydrolyzed but they may be fermented through
colon microbiota present in lower GIT [26]. Digestible and hydrolyzed
dietary fibers can be utilized for the for-better impression in the fate of
carbohydrate nanoparticles in GIT in respect of unlike toxicity [43, 46].
Moreover, non-hydrolysable carbohydrate NPs can interact with colonel gut
microbiota and can imply to some adverse health effects by changing the
availability and activities of the nanomaterial.

1.3.2 INORGANIC NATURAL AND ANTHROPOGENIC NPS IN

FOODS

Presently, the NPs in the food industry are made of inorganic materials.
Basically, these are noble metal NPs (Ag and Au) and metal oxide NPs
(Fe3O4, Fe2O3, TiO2, SiO2 and ZnO2). Synthesis of these NPs defines the
crystallinity (crystalline, amorphous, and polycrystalline), morphological
aspects (spherical and non-spherical) and their surface properties at ambient
temperature. NPs size and shapes also depends upon the precursor materials
and fabrication conditions. Dissolution tendency of inorganic NPs also
differ in diverse parameters of solution (e.g., solution pH and solution ionic
Stability and Fate of Nanoparticles in Foods 13

strength) as well as their biochemical reactivates, which possesses the key

role over their GIT fate and harmfulness.

1.3.2.1 FOOD ADDITIVE SILVER NPS

Mainly AgNPs are applied in food for both additive and packaging. Along
with antimicrobial property it has good antibacterial, antifungal, antiviral,
and anti-algal activities. Therefore, it can increase the self-life property of
food is added to food and microbe free containers. AgNPs may migrate from
these packed containers to the edible foods and could be swallowed in the
digestive system and transferred impulsively to the biological media like
GIT juices and foods.
In the USA, foods, and beverages are delivered in specific bags and
containers, namely, Kinetic Go Green basic nano-Ag container for food
containment, Oso fresh food loading package [10], and Fresh LongerTM
Plastic storage containers [4]. Thus, some studies responding that AgNPs
have revealed no toxicity despite other studies reporting appreciable level
of toxicity. It is estimated that mostly adults and children are eating about
20 and 80 µg/day of Ag, amounting only for good fraction NPs. There are
several studies available on animals’ consumption of AgNPs which causes
lymphocyte penetration, coloration of villi, and discharge to mucus granules,
with unusual mucus composition. AgNPs can be accumulated in various
organs after consumption, including small intestine, liver, kidneys, spleen,
and stomach.
To date, a number of studies have been reported on cell culture models
where the cytotoxicity is reported to be promoted by AgNPs through several
mechanisms. It is revealed through cell culture experiments that AgNPs with
smaller sizes are said to be more toxic in nature than that of bigger sized NPs.
AgNPs contributes to the toxicity through the ROS production that leads to
oxidative stress and hence the damage of cell by harming cell membrane,
inner cellular organelles as well as nucleus. Normal biochemical functions
viz. ATP (adenine triphosphate) production, replication, expression of the
genes may be altered by such mechanisms. Gut microdata nature could also
be altered as AgNPs have a strong anti-microbial activity, if reached to colon.
In some cell culture studies, researchers have ignored the effect of
AgNPs on food matrix, but according to the recent reports, AgNPs have been
explored as a potential candidate to toxify the intestinal cells. As obtained
outcomes estimated that AgNPs can be engrossed by GIT into the complete
14 Nanotechnology Horizons in Food Process Engineering, Volume 3

circulation and confirmed the distribution in several body tissues and organs.
Though, very less amount of <1% of consumed silver nanoparticles (AgNPs)
are collected in our body organ and commonly defecated in feces and urine
after administration doses of about 200 and 250 mg/kg body weight for
single and multiple sittings and not any adverse effect were observed. In one
more oral gavage of feeding of rat no major toxic effects were found. But,
after the ingestion of AgNPs over a 28-day period (30, 300, and 1,000 mg/
kg day), high doses some slight liver damage and it was observed in some
of studies reported about the adverse impacts at high level doses. Indeed
125 mg/kg ingestion of AgNPs may be the critical limit for the ingestion of
AgNPs and above which adverse effects on liver was observed.

1.3.2.2 FOOD ADDITIVE ZINC OXIDE (ZNO) NPS

Inorganic ZnO NPs are used mostly in packaging to detour micro-organism

and provide contamination free food, show antimicrobial property against
pathogenic bacteria or can absorb the ultraviolet (UV) light from the UV
sensitive foods. Zinc accounts for an essential trace element in NPs to sustain
healthy wellbeing and is most often used as a supplement in functional
foods. Packaging may leach out into the food items, thus if ZnO NPs after
packaging leach out then it can act as a supplement and can be ingested as
the part of human diet. However, it should be in a balanced manner, a current
risk assessment advises that ZnO NPs could not arise to a considerable level
[33, 86].
The ZnO NPs anti-bacterial activity revealed that ZnO NPs are accu­
mulated in the microbial cell through cell membrane penetration channel
and as result ROS production takes place which leads to the cytotoxicity
[68, 82]. ZnO NPs if accumulated in excess amount in the human body
could lead to the severe health issues [81]. One study revealed that ZnO NPs
single oral dose could cause hepatic injury, kidney problems and lung infec­
tions. Remarkably, one study also displayed that ZnO NPs could not have
toxic effect if utilized in isolation. Interestingly, ZnO NPs have cytotoxic
in combination with ascorbic acid and cytoprotective effect in combination
with casein phospho-peptides [27]. These reports on ZnO propose that zit is
significant to quantify the impact of certain food ingredients toxicity level in
combination with ZnO NPs.
From morphology point of view ZnO NPs could be spherical as well as
non-spherical solids in shape and in some cases, hollow nanostructures as
Stability and Fate of Nanoparticles in Foods 15

well. ZnO NPs have the tendency to aggregate in aqueous solutions swiftly
[11, 80]. Aggregation of ZnO NPs depends upon the population, i.e., concen­
tration of NPs in the solution, shape, size, structure, and solution environment.
Higher concentration and lower particles size lead to higher aggregation.
Aggregation of NPs could be the reason for the toxicity and their GIT fate.
In the recent study, two sets of frogs were fed with equal amount of ZnO
NPs, and zinc doses were given to each frog. Findings suggested that pure
ZnO NPs were found more toxic than that of pure zinc powder, i.e., ZnO NPs
possess high oxidative cell damage than that of pure zinc [39]. Hence, the
pure form of zinc is more important than that of ZnO NPs.

1.3.2.3 FOOD ADDITIVE IRON OXIDE NPS

In various foods and beverages, the bioavailability of iron as well as color

providing component is supplied and maintained mostly by iron oxide [30,
51, 60]. In USA, the usage of iron oxide, as a food colorant, is highly limited
and approximately 0.1% by weight is used in sauces. According to the recent
research, 450 µg/day iron oxide is taken by the consumers from all types of
dietary products if a consumer takes minerals containing fortified foods and
functional supplements as well because in such supplements the concentra­
tion of iron oxide remains higher [51]. Therefore, it could be noted that the
average intake of Fe is noted to be around 10–23 mg/day [2].
There should be focus on in which form nanomaterials are administered
as the iron oxide particles are not delivered as such as the iron oxide. Nano­
materials may change their identity in respect of sizes, shapes, and crystal­
linity, and this may affect its working efficiency and toxicity variously. It has
been also reported that the iron oxide. Nanomaterials produces ROS which
can impose the potential toxicity [82, 87]. In an experiment, about 3 mg/kg
body weight iron oxide nanoparticles were administered through gut in the
rat for over a 13-weeks and it was found that rats did not accumulate iron
oxide particles in tissues or produce toxicity [20]. In another experiment, rats
were administered with much higher oral doses of 250–1,000 mg/kg body
weight for 13-weeks without any tissue accumulation or toxicity [40].

1.3.2.4 FOOD ADDITIVE TITANIUM DIOXIDE NPS

Titanium oxide is a white powdered metal oxide material at nano range and
is utilized as the food additive material. Nanocrystalline food grade titanium
16 Nanotechnology Horizons in Food Process Engineering, Volume 3

oxide NPs are mostly in the form of anatase and rutile in polymeric form
having different crystal and physicochemical properties [90]. It is categorized
as the food additive so it can provide a whitening effect and highest content
present in candies, sweets, beverages, and chewing gums. A single chewing
gum leads to an intake of 1.5–5.1 mg of titanium oxide NPs [15, 83]. Higher
amount of it is consumed (2–4 times) by the children [3]. The configuration
of various food-grade titanium oxide NPs varies depending upon its source.
Titanium oxide NPs source also contains certain level of aluminum, silica,
and phosphorous [64]. When titanium oxide NPs are optimized to have
particle size ranging between 100 and 300 nm, it increased their lightening
and light scattering properties [36].
In most of the studies for various food applications mean diameter of
titanium oxide (E171) powder NPS from several manufacturers have been
recommended to be 110 nm, while, mostly the size remains below 100 nm
[18]. In USA and UK, the estimated dietary exposure of humans to tita­
nium oxide NPs has been testified from 1.1–2.2 mg/kg body weight/day
[51]. Similar to other NPs titanium oxide NPs could differ in size, shape,
morphology, surface properties and crystal structure that have bad impact on
GIT fate and toxicity after aggregation [25, 51].
According to the study on the intake of titanium oxide NPs for 16 rats,
the higher concentration and accumulated titanium oxide NPs were magni­
fied in spite of slow elimination rate [38]. Rodents acute and sub-chronic
reports on titanium oxide based on oral delivery of 25, 80, 155, 5,000 mg/
kg body weight, resulted in the accumulation of NPs in spleen, liver, kidney,
and lung tissues which leads to the nephrotoxicity and myocardial damage
[67]. Titanium oxide NPs (5 nm, anatase crystal phase) were administered
intra-gastrically to mice for 30 days @ 62.5, 125 and 250 mg/kg body weight
[8]. Resultantly, higher dose causes damage to liver function, hemostasis
blood system as well as in immune responses [72]. Interestingly, when tita­
nium oxide NPs constituting of anatase and rutile with a size of 21 nm were
administered, there were no significant toxicity or accumulation reports
indicating the secretion of all titanium oxide. The experimental paradoxes
among diverse animal studies on the build-up and harmfulness of titanium
oxide NPs may arise in significances of a number of reasons.
Primarily, NPs size, shape, crystal phase, agglomeration state, and dose
supplementary route could be toxicity reasons of titanium oxide NPs used in
the study. Secondly, the influence of food matrix and GIT channel on NPs are
frequently overlooked or taken in different manner. Lastly, the methodology
to conduct the animal study to know the toxic effect of titanium oxide NPs
Stability and Fate of Nanoparticles in Foods 17

based on accumulation of titanium oxide NPs and selection of animal model

can differ.
Age of animals age plays an important role to know the cytotoxic effect of
NPs. Equal amount (200 mg/kg by body weight) of titanium oxide (anatase)
NPs was given to rats of 3 weak old and 8 weak old and both the sets of rats
were incubated for 30 days. It was observed that young rats (3 weak old)
were more affected than older ones in terms of liver swelling, heart injuries
and stomach tissue damage.
Titanium oxide NPs with anatase crystal phase have observed more
harmful effects than that of rutile crystal phase, which could be due to the
photocatalytic activity of anatase phase. Recently, it is reported that pure
form of titanium oxide (anatase or rutile crystal phase) are more toxic than
their mixtures. Pure anatase or rutile give cytotoxic and genotoxic related
damage.

1.3.2.5 FOOD ADDITIVE SILICON DIOXIDE NANOPARTICLES

Conventionally silicon dioxide nanoparticles for food additives are prepared

by using amorphous silica [92]. Researches have reported that uptake of
about 124 mg per day of SiO2 NPs could be the characteristic intake dose in
human [17]. In daily routine habit of consumption of food like noodles, rubs,
soups, and coffee creamers mostly contain SiO2 NPs. Some studies showed
that the SiO2 NPs accumulates in organs such as liver, but such accumulation
does not address any potent toxicity [53]. Few studies indicate the subcel­
lular exposure of silicon dioxide nanoparticles which could result in damage
to the organs, glutathione depletion, DNA (deoxyribonucleic acid) damage
is through the mechanism of activation of the MAPK/ERK1/2 and Nrf2/ARE
(antioxidant response element) pathways [32].
One of the researches reported that the oral administration of 2,500 mg/
kg body weight of SiO2 NPs in rats per day continued for 84 days distributed
and accumulated the nanoparticles in different rat body organs like lungs,
kidney, and spleen. Analysis of exposed rat’s accumulated organs by induc­
tively coupled plasma-mass spectrometry (ICP-MS) showed there were no
silicon dioxide nanoparticles found in the liver. However, 84 days exposure
detection through histopathological examination and gene expression studies
revealed the live fibrosis [93].
SiO2 NPs are used as additive to powdered foods as the anticaking agents,
which consequently enhances the flow properties of such food materials.
18 Nanotechnology Horizons in Food Process Engineering, Volume 3

One of the food grades SiO2 nanoparticles is E551 having particle size 100
to 1,000 nm and may pollute water bodies with its smaller sized particles.
Predictable intake of SiO2 is in the scale of 20–50 mg/day per person. Certain
reports show that single SiO2 nanoparticle having a diameter of about 10 to
50 nm but it clusters to form large aggregates usually 100–1,000 nm. During
in vitro and in vivo studies, administration of SiO2 NPs at high levels resulted
in hostile effects like cytotoxicity and ROS generation.
The latest study advised that SiO2 NPs when collected in the liver it get
accumulated at those critical limits with a potential health risk. Feeding of
amorphous SiO2 NPs to mice at the rate of condenses doses daily up to 10
weeks increased the amount of ALT (alanine aminotransferase) and resul­
tantly creates adverse effects on the liver. Conversely, in one of the studies
of oral doses of SiO2 NPs in rats up to 13-weeks reported no accumulation
or toxicity. But across a realistic exposure range when pristine SiO2 NPs
shows the adverse dose-responsive effect on cell culture model of intestinal
microvilli of human GIT in sense of ROS production. Therefore, we cannot
clearly conclude the toxicity of SiO2 NPs drawn on the basis of available
data.

1.4 COMPLEX NANOPARTICLES IN FOODS

Complex nanoparticles or material are formed mostly in natural environment

which cannot be classified neither purely organic nor inorganic or mixed
hybrid phase. Its formation may be through dissolution, aggregation, or
agglomeration of the nanomaterial precursor in a same phase of platform.
Ample of precursor combinations of organic carbohydrate, lipid, and protein,
inorganic precursor ions of metals, metalloid or non-metals in the symphony
of interactions in the presence of certain features of temperature, pres­
sure, lighting or thundering may create the complex nanoparticles. Mostly
complex NPs are present in nature, but synthetic or engineered nanoparticles
are also present.
Coacervates (CCs) are naturally formed in nano-ranged particles and
these are generated by the electrostatic interactions of the charged proteins
and polysaccharides [63]. Lipidic nano range particles are coated in the lami­
nated coat formed by the successive electrostatic interactions of the charged
biopolymer into the lipid droplet. The prominent fate of the ingested droplets
is that they remain non-digestible if the coating remain intact and help to safe
intact materials inside to achieve the target.
Stability and Fate of Nanoparticles in Foods 19

Complex foods comprise of mixed charged biopolymers, these biopoly­

mers may be oppositely charged. However, if the biopolymers are oppositely
charged than they may also form a complex structure. In industries complex
food may be also created in the presence of protein in precursor solution
having low isoelectric point towards positive charge and having mixture of
gelatin or gum Arabic (GA). Complex NPs contains within cross-linking of
glutaraldehyde or transglutaminase and polyphenols.
The properties of complex NPs as the CCs is encapsulation of flavors,
water-soluble bioactive molecules and essential oil also. Complex NPs CCs
are manipulated on the accordance of need for pH, ionic strength, concentra­
tion, and ratio of the two polymers by using the phenomenon of bottom-up
approaches to nanotechnology. Complex CCs are the driven through forces,
whereby the primary deriving force is electrostatic interactions, hydrophobic
effects and hydrogen bonding. Hydrogen bonding often acts as the secondary
parameter for the stabilization of CCs. Organic-inorganic types Chitosan-
ZnO complex nanoparticles have the intrinsic antibacterial properties against
gram positive Enterococcus faecalis and gram negative E. coli bacterial
species [56].
In a study, complex nanoparticles are sonochemically deposited on
the cotton and applied for on the cotton fabric. Moreover, Carboxymethyl
chitosan-soy protein complex nanoparticles are successfully synthesized by
few researchers and employed for the successful vitamin D delivery system.
The average particle size of these complex NPs exhibited in range between
162 and 243 nm. Complex NPs also possessing the desired stability and solu­
bility after centrifugation and lyophilization [75]. Nanoparticles also affects
the bacteria cell morphology through enhanced free radical effect [41].

1.5 PATHWAY OF FOOD ADDITIVE NPS THROUGH INTESTINAL

NPs are mostly found ubiquitously in every food which is ingested in GIT
either in natural or synthetic way. Human beings and other living organisms
are exposed to NPs from evolutionary phase through food. Due to the large
population, huge diversity in food and large spectra of NPs, it is difficult to
define clearly how NPs are being introduced into living system. Mammalian
GIT with approximate 5 meters is extended from stomach to anus in humans
[9]. Compartments of GIT are stomach, small intestine and large intestine
which all are compartmentalized and interconnected through passage called
sphincters.
20 Nanotechnology Horizons in Food Process Engineering, Volume 3

The functioning of these compartments include: digestion, homeostasis

maintenance, absorption of macro and micronutrients, electrolytes from
the food and immunogenic responses against the pathogens. The various
compartments of the digestive system are shown in Figure 1.4. Not much
information is available in the literature on the uptake of NPs on the surface
epithelium layer of buccal cavity and esophagus. But macromolecular and
for nano-particular selective uptake in the intestine are specialized. Surface
area of the stomach is about 0.05 m2 that is comparatively less than the
surface area and permeability of the macromolecules is allowed through
gastric epithelium then the minimal passage of NPs [9].

FIGURE 1.4 Various compartments in the digestive system.

Stability and Fate of Nanoparticles in Foods 21

When NPs encounter epithelial cells of GIT, they first come in contact
and cross to the mucus barrier. The mucus barrier is the bed of mucus which
is the constituent of mucin glycoprotein having viscoelastic gels property
which resulting to an adherent unstirred layer behavior of coating on Gastro­
intestinal wall. Mucus layer is tightly bonded on the surface inner sidewall
of the stomach and large intestine. Out of digestive effluent substances that
get trapped on the mucus layer get hindered and other un-trapped effluent
get diffused through this mucus layer. Small intestine is containing thinner
mucus layer so low hindrance of effluent uptake between the lamellar strings
occurs that allows greater access of the luminal contents to the epithelium.
Indeed, mucus thin layer in small intestine permits more fluently uptake of
nutrients than trapping, immobilizing, and excluding.
Three successive parts of the small intestine are duodenum, jejunum, and
ileum. Small intestine is the longest segment of the GIT and in the inner
luminal side the microscopic finger like projection structured layer is present
called villi and microvilli resulting into the very high surface area of 30
m2 in humans. Its surface is made up of epithelial monolayer and having
tight but selective barrier to maintain homeostasis. The epithelial monolayer
containing several types of specialized cell of Enterocyte cells are respon­
sible for nutrient absorption, while other cell performs for the secretion of
mucus. Large intestine (colon) has the haustral folds rather than villi projec­
tions but haustral folds are shorter and having low surface area of 2 m2.
Enterocytes are intestinal absorptive cells that are having columnar epithelial
cells and are present on the inner luminal surface of large and small intestine.
Columnar enterocytes in the epithelium are the predominating type of cell
in the GIT.

1.5.1 TRANSPORTATION MECHANISM OF NPS THROUGH

EPITHELIAL CELLS

To understand the fundamental understanding of NPs absorption in the GIT,

we need to understand the indulging of the nanoparticles in the various
microscopic routes. From the available information, we can say that the
particulates material can be taken up during all digestion through two
trans-epithelial routs. These routes allow the passage of substance transport
through cellular or para-cellular transport that is with in epithelial cells or
between adjacent epithelial cells, respectively, and can be bi-directional also.
22 Nanotechnology Horizons in Food Process Engineering, Volume 3

Absorbed effluents in GIT from the surface apical membrane to cell cyto­
plasm can follow the several fates. Perhaps the fates of the nanoparticulate
material can be the secreted back into the lumen, or it remains accumulated in
the cell, or may transport across the basolateral cell membrane into systemic
circulation. There is steric hindrance and immiscible solubility created in the
small milieu of particulate matter during absorption, which limit the amount
of simple diffusion of particulates in the cells. Carrier-mediated transporters
are a small molecular ligand that takes up specifically small molecule but are
not specific to larger NMs. There are various transporters =in the epithelium
of the GIT out of which vesicular transcytosis are the efficient mechanism
to transport intact macromolecule or nanomaterials within or across the cells
via energy dependent process.
Many types of nanomaterials dynamically interact with actin cytoskel­
eton, microfilaments, and microtubules and follow the process of transporta­
tion. When ligands in content of intestinal lumen receptor protein-mediated
endocytosis of clathrin or caveolin through receptor-mediated endocytosis,
process called vesicular transcytosis. It triggers the exterior of the apical cell
membrane to endocytosis than the lower will be the endocytic activity of
NPs translocate is considered to be lower.
Nanomaterials to be endocytosed has been reported as ferritin metallo­
protein and tartrate-modified ferrihydrite through pinocytosis and micropi­
nocytosis, non-selective mechanism of endocytosis. Lymphoid follicle and
Peyer’s patch M-cells of GIT uses both phagocytosis and receptor-mediated
endocytosis to sample lumen contents. Phagocytosis is the process of
engulfment solid particles of viruses, bacteria, or particulate matter through
the cells. Intracellular vesicles of pinocytosis or micropinocytosis fuse to
lysosomes containing enzymes for enzymatic degradation of the phagocy­
tosed contents. Thus, it is usually understood that majority of nanoparticles
endocytosed in the GIT proceeds by one of these routes. Out of using any
energy passive transport of solutes occurs through epithelium layers called
paracellular transport by the tight junctions binds between cells together into
a monolayer (Figure 1.5).
Notably, majority of transporters participate in the absorption of intact
nanomaterial in the gastro epithelial viable M-cell of intestinal lining
in Peyer’s patches and are present abundantly in intestinal enterocytes.
Therefore, it is important to understand the complete information about
transportation in GIT because some digestive material may release ions after
degradation which may get absorbed into the body, and these ions may act
as the precursor to reconstitute to form nanomaterial. These constructed
Stability and Fate of Nanoparticles in Foods 23

Nanomaterials can be either intact uptake in GIT or may follow the partial
or complete degradation through the cytosolic release of the epithelial cells.
Degraded nanomaterials may either pass into the underlying lymph fluid or
may remain intact and circulate through the lymphatic system with lymphatic
fluid.

FIGURE 1.5 Effect of nanoparticulate material on epithelial wall and transcription of IL-8
mRNA and its translation to secrete IL-8 chemokines.

From lymphatic system, NPs eventually are channeled to either systemic

cardiovascular circulatory system or may be absorbed directly into the blood
capillaries. Capillaries are helpful in transferring the oxygen and nutrients
with blood. Buccal cavity wall and esophageal comprises of blood capillaries
that lead into systemic circulation. Some GIT absorbed can again comeback
into intestinal lumen through secretion of capillaries via enterohepatic circu­
latory system and bile from gallbladder. Nanomaterials are also distributed
to systemic tissues where they may be metabolized or enter in the excretory
system to be excreted out in urine or sweat out from external skin.

1.5.2 ABSORPTION OF NPS IN GIT

A limited number of publications are available on the in-vivo studies

of mammalian GIT NPs absorption and its quantification. In this section
the discussion shall be revolving around the absorption behavior of the
24 Nanotechnology Horizons in Food Process Engineering, Volume 3

nanomaterial in the body tissues. Three certain examples of titanium oxide,

silicon oxide and AgNPs that are possibly the most food-applicable NPs
have been discussed thoroughly to address most of the tissues related to the
absorption and potential behavior of the nanoparticles in the food. However,
there is not appropriate number of studies sufficient to allow an exact
inference, but few proposals of research work reveal that low percentage
of administered titanium oxide and SiO2 nanomaterials adsorbed in mamma­
lian circulatory system of blood and peripheral tissues inspire majority of
nanoparticulate materials expelled in the feces [89].
Titanium oxide nanoparticles of 500 nm are measured for the percent
absorption in rats and exemplified during the orally exposed by gavage for
10 days. Microscopy visualization and necropsy study of NPs were done in
intestinal Peyer’s patches and observed. During the spectroscopic analysis
in the stomach, about 0.11% and 4% of titanium oxide nanomaterials were
quantified in the small and large intestine, respectively, and 2.86% and 0.02%
was found in the Peyer’s patches after accumulation in blood lymphoid
tissues accordingly [16].
Other similar experiment was conducted in a mouse with Anatase tita­
nium oxide NPs of 12 nm for 6 h consequently single gavage exposure in rats
titanium oxide get agglomerates and some were quantified in cytoplasm and
lower area of the cells [8, 12]. Therefore, the passage of either particles or
dissolved form of titanium oxide was ventured. As per the limit of detection
(LoD) of the imaging technique, the quantity of NPs in the tissue was below
the 30 parts per million (ppm).
Another study of administration of amorphous (7 nm), agglomerates
(10–25 nm) SiO2 NPs was followed in the rats through their feed for 28 or
84 days was having absorption through peripheral tissues in GIT was less
than 0.25%. SiO2 NPs are either absorbed intact or have occurred from the
silicic acid (act as the signaling molecule) released from the particle surface.
Moreover, it was found that the percent absorption decreases as the doses
increases due to agglomeration silica particles converted to gel in the lumen
[9]. These above studies mechanisms of titanium oxide and SiO2 Nanomate­
rial advised by the data that transportation is continued through transcellular
and paracellular via phagocytosis through M-cells of Peyer’s patches with
disintegrated molecules that may release from the particle surface accord­
ingly. Paracellular transport of intact particles may occur through damaged
breaches of the epithelial cells, and per-sorption of intact particles through
dead epithelial cells [52].
Stability and Fate of Nanoparticles in Foods 25

Silver NPs having antimicrobial activity and after ingestion it may modify
the composition of intestinal microflora. To address the issue Silver NPs
(2–7 nm) was administered to a model poultry animal the quail for over 12
days in drinking water at the coinciding doses of 5, 15, and 25 mg Kg–1. The
investigators found that there were no major changes in quail gut microflora,
but the highest dose of silver NPs increases the population of lactic acid
bacteria in the cecum [52, 65].

1.5.3 EFFECTS OF GASTROINTESTINAL LUMINAL FACTORS ON

NPS (SIZE AND SURFACE PROPERTIES)

The examination of the structural properties of the GIT wall, reveals the pres­
ence of four different layers: the inner luminal side is the mucosa, submucosa,
muscularis propria and the outer most side of lumen covered with Adventitia
(or serosa). Mucosa is the covering layer of the luminal cavity that come in
direct contact with digestive food, its innermost luminal side is of epithelium
layer. Superficial epithelium layer cells produce the two-layer of mucus
system that is the cellular attached mucus and the upper loose mucus layer
towards the lumen cavity. Mucus is a viscoelastic biological hydrogel that
protects the epithelial surface from penetration by most NPs. Adventitia (or
serosa), the outer most layer of the wall contains blood vessels, lymphatics,
and nerves. Indeed, administered NPs property effect is depends upon its
size, shape, aggregation, and surface property.
First encounter of Nanomaterials occurs with mucus which creates the
NPs and interacting mucus corona. Hydrophobic NPs are absorbed more
readily than the hydrophilic nano particulates with few exceptions [7].
Therefore, when polyethylene glycol is a hydrophilic molecule when coated
on nanomaterial, it emphasizes to enhance the bioavailability and stability
during in vivo digestion [77]. Much adhesion may trap to limit NPs by
confining it to pass epithelial absorption [7]. Moreover, few lectin proteins
bearing nanoparticulate material like wheat germ agglutinin protein have
interacting behavior with intestinal enterocyte receptors that can facilitate
the entry through the cellular obstruction [94], lipid-coated Nanomaterials
can also show this behavior [78].
Mucus layer is having negative surface charge and it can affect the
nanoparticulate adhesion property, depending upon its surface charge
behavior. As well as along with NPs surface charge property, size has the
determining feature for mucus layer transit, less sized particulates can more
26 Nanotechnology Horizons in Food Process Engineering, Volume 3

freely pass the mucus bed thread network pore to rich muscularis propria [6].
During digestion, there is degradation of the food through digestive juices,
dissolution, and accumulation can exclude such any nano-sized non-needful
materials in different compartment of GIT with various parameters which
provides significant response with Nanomaterials and uptake.

1.5.4 IMPACT OF PHYSICAL FORCES IN GIT

During digestion process most forces are chewing and mastication in mouth
and peristaltic waves developed in GIT wall helps to go down masticated
food-bearing Nanomaterials towards the stomach. The frequency of peri­
staltic forces in the stomach can be measured in the manometric unit of 5–20
mmHg pressure [9]. ENMs or natural Nanomaterials may release from food
matrices during these transits encountered with these physical forces. On
the other hand, research related to peristalsis forces can somewhat affect the
digestion and accumulation of cellulose NPs in a colloidal suspension of
masticated food [9]. But no research was found on strong chewing force on
the food with relevant NPs.

1.5.5 INFLUENCE OF OSMOTIC CHANGES (IONIC STRENGTH

AND PH) ON GIT NPS

Variable compartments of GIT shown in Figure 1.4 having the content of

fluid-filled with solutes which is having precipitative behavior like salting
out to precipitate NPs. Synthesis of NPs depends upon the presence of
charged ions and stability exists on the development of surface charge
with magnitude of electronic repulsion and zeta potential. Modifications in
these these property determines the growth and size of the NPs [13]. In the
digestive system pH of the compartments vary from the buccal cavity to the
rectum as well as it also changes in lumen effluent with mucus layer.
Therefore, difference in ionic create change in pH and the NPs that can
be developed have the influence on the surface charge and aggregation. For
example, on the surface of titanium oxide NPs divalent cations get adsorbed
through the water which neutralizes their negative charge and induces aggre­
gation. Like if sodium chloride concentration is present in fluid suspension of
GIT can suppress the electrostatic repulsion on the surface of titanium oxide
nanoparticles and that agree to form van der Waals interactions resulting in
an increase in aggregation rates of particles [96].
Stability and Fate of Nanoparticles in Foods 27

In vivo, in different GIT compartments, the parameters are dynamic,

which simulates to create same molecule, but various NPs and in vitro
various compartments shows changes after transits. Like if SiO2 NPs admin­
istered in salivary fluid in food matrices a small aggregate appears. For the
evaluation of stomach gastric digestion solution is having pepsin enzyme
in mammals with pH-2, where titanium oxide NPs (with positive surface
charge) and SiO2 NPs (neutral) shows the agglomeration to significant larger
clusters followed by the successive enhanced secretion of solution in the
intestinal digestion. At pH-7 the digestive enzyme and bile salts originated
nanoparticles have a negative charge and saliva developed SiO2 agglomerates
get de-agglomerated reverse to the nanoparticulate size range. Thus, in the
condition of low pH and high ionic strength in stomach NPs get aggregated,
but no aggregation was observed at high pH digestive juices. Hence, the pH,
ionic strength collectively osmotic concentration can influence and play with
the surface and size of nanoparticles [35].

1.5.6 INFLUENCE OF ENDOGENOUS BIO-CHEMICALS AND

FOOD MATRIX BIO-CHEMICALS ON GIT–NPS

GIT NPs interacts in an appropriate milieu of endogenous and ingested bio­

chemicals materials and its collectively exposure exchanges the morphology,
magnitude, and surface criteria for example soy oil emulsion when coated
with β-lactoglobulin protein NPs in water, come with artificial saliva, free
mucin proteins bridge the NPs to blot out of the suspension. Instead, when
pectin, a plant product added on the coating of emulsified soy oil that increases
the electrostatic and steric repulsive forces to stabilize the nanoemulsion [8].
Gall bladder bile duct consisting of bile salts and phospholipids, which
are the compound most active on the surface of digestive effluent in the
intestine that affects the colloidal behavior. Bile duct when excluded to small
intestine it also facilitates the thermodynamic stabilization of free fatty acid
which are released from triglycerides after its digestion to submicron mixed
micelles. Similarly, the bile duct is also activated upon the ingested NPs. For
illustration, if bile salts are arranged to adsorb on the nanoemulsion of almost
500 nm size range, increases the diffusion through the intestinal mucosal
layer. Nanoemulsion can be made up of bovine milk protein, caseinate, and
medium-chain triglyceride oil. Mucus layer molecule is having negative
charge and artificially bile salt surface absorbed NPs reduces the cohesive
electrostatic forces of mucus network to simplifies the convey of NPs.
28 Nanotechnology Horizons in Food Process Engineering, Volume 3

Therefore, bile salt can be utilized when surfactant adsorption to enhance

the passage through the mucosal network of soft lipidic nanoparticulate
materials as well as non-lipidic NPs [47].
The component of bile salt phospholipids secrets to form variable
concentration throughout the digestive canal. Phospholipids are the zwit­
terionic surfactants contributes to decrease the surface tension emulsification
and solubilization of lipophilic materials. Other organic endogenous bio
molecules lipid, carbohydrate, protein, nucleic acid, and dietary fibers can
be used for the surface adsorption with binding affinity for the nanoparticles.
Binding affinity dependents upon the stoichiometry and pK value of the
interacting proximal milieu.
Various factors of digestive fluids, organic matter, exogenous surfactant
involved in the controlling the particle size of titanium oxide and carboxy­
methyl cellulose nanoparticulate aggregates. Sometimes mixture of biomol­
ecules like proteins and bile salts if binds on the surface of titanium oxide
or SiO2 it accelerates their aggregation in the intestinal aqueous digestive
fluids. But when SiO2 nanoparticles encounters the food matrix of low fats,
cream the particles restricts to aggregation. Therefore, the biomolecules
present in the luminal tract of the digestive system can change the properties
of nanoparticulate materials.

1.5.7 INFLUENCE OF NPS ON PHYSIOLOGICAL VARIABILITY

AND DISEASES

When NPs influences the normal physiology of digestive tracts, the definite
environment may be altered in the existence of some diseases in respect
of continuous cellular exposure of NPs and may also affect cellular perme­
ability. So, this research area should be considered as the prior field of
research study about the NPs being administered in the food and its further
consequences. Physiological variability in digestive system is influenced by
many factors one of these is age of human, different aged group peoples
have different pH, transit time of fluid presence of barrier in lining changes
in compartments [61].
With age and gender of the person the response to various disease initi­
ated by the consumption of the nanoparticles may also vary. In one of the
research male rats were orally treated with spherical 26 nm titanium oxide
NPs for 90 days. Next after blood examination it was found that the level of
titanium was increased up to approximately 1.25-fold but negligible amount
were remarked in female rates [73].
Stability and Fate of Nanoparticles in Foods 29

Women during pregnancy may also have different response in digestive

system physiological viability in awe of disease of gastroesophageal reflux,
inflammatory bowel, peptic ulcer and irritable bowel syndrome. The factors
of age, gender, malnutrition, sleep cycle, pregnancy, and stress change the
pickup behavior of NPs than the normal digestion, NPs which are used to
supplement in the in food to rejuvenate the body [23]. Moreover, stress may
affect the digestive system in sense inflammatory response and may increase
the permeability of GIT lining [48].
Crohn’s disease and ulcerative colitis are common inflammatory bowel
diseases of GIT in which the mucus layer become abnormal and the tissue
associated with this disease outcomes to enhances the liable uptake of
nanomaterials [37]. For conformation in a mouse model studies of ulcerative
colitis nano range SiO2 particles found to be attached in the ulcer area in
inflamed tissue [31].
The retrospective study of Crohn`s disease, ulcerative colitis and colonic
carcinoma surgically removed from human volunteers. Microscopy of
lymphoid aggregates and Peyer’s patch tissues from normal tissue of the
small and large intestine was observed and found that 100–200 nm titanium
oxide and other inorganic elements of silicon, potassium, sodium, magne­
sium, and iron of about 100–700 nm were found in phagolysosome via
macrophages of epithelium cells [76]. Celiac disease, gastroenteritis, and
additional autoimmune disease are also associated with abnormal gastric
functioning. Gastroenteritis is related to gut permeability which is increased
in this disease and causes microbial infection of enteropathogenic Esch­
erichia coli (E. coli), Campylobacter jejuni, Yersinia pseudotuberculosis or
Clostridium difficilie. Out of which in humans Yersinia pseudotuberculosis
infection is observed to increase the transcellular micropinocytosis and was
detected through with 200 and 500 nm polystyrene beads [59]. Therefore,
the human subpopulation have difference in physiological properties in the
gastric intestinal tract can show the effect on certain abnormalities, lesions,
cancer tumors and trafficking of nanoparticles are also interrogated.

1.5.8 INFLUENCE OF COMMENSAL MICROBES ON GIT–NPS

Whole GIT harbored with an extremely complex microbial flora is very

much helpful to fulfill the requirement of cobalamin (vitamin B12). With
this non-pathogenic microbiota supports for the probiotics and fights with
pathogenic microbes to create balance, it also helps to maintain homeostasis
30 Nanotechnology Horizons in Food Process Engineering, Volume 3

and gut-associated immunity. Approx. 1,000 different species of microorgan­

isms were identified during the sequencing techniques of bacterial genetic
material which can be affected by the nanomaterial. Gut-associated bacterial
system is not involved in any activity for direct endocytic mechanism of
nanoparticulate materials but cohesive with the food persistent NPs indi­
rectly through microbial secretions.
But during in vivo condition culturing of gut-associated microbes secretes
enzymes that acts on the integrity of digested NPs. The gut-associated
anaerobic bacteria and fungi secrets cellulase is purified and then applied
on nanoscale architecture of cellulose microfibers and it becomes partially
digested. In addition, SiO2 and carboxymethyl together forms cellulose
particles which are expressively hydrolyzed with secreted cellulase enzyme
[8]. Limited work is available on the hoe the gut-associated microbiota is
influenced by the novel NPs, and needs more attention from the research
community.

1.6 IMMUNOGENIC PROPERTIES OF INGESTED

NANOPARTICLES

The immune system is the human body defense mechanism, which comprises
many biological structures and is composed of two branches of the lymphatic
system and lymphocytes. The organs of the GIT immune system include the
spleen, lymph glands and lymph nodes in the mesentery of the intestine, peyer
patches, and space between the epithelial cells of the mucosa and cells of
the immune system consists of lymphocytes, dendritic, and macrophages as
cells of the immune system. These immune system cells are found in the area
beneath the intestinal epithelium said to be lamina propria and in additional
reside within lymphoid follicles. Lymphocytes remain immature until they
come in contact with antigen. Lymphocytes are of two types depending upon
their origin in bone marrow or in thymus gland that is B-cells and T-cells
respectively. Mainly Immune system functioning involves recognition of
invading antigens with the recognizable connecting link epitope present on
the pathogenic microorganism. Most macromolecular antigens or microbes
are held at the cove of the intestinal villi to absorb the nutrients efficiently.
Gut-associated lymphoid tissues (GALT) are the major frame of lymphoid
tissue are situated and extended in the inner small and large intestinal
luminal wall. It is sequestered to aggregate the lymphoid follicles known as
Peyer`s patches. GALT are the component of the immune system having a
Stability and Fate of Nanoparticles in Foods 31

specific type of epithelium microfold (M)-cells and enterocytes, thin mucus

layer. M-cells confine to the sampling of antigens and are about 1% of the
intestinal cell lining.
In the intestine, Titanium oxide NPs induces the release of cytokines that
gives inflammatory response and lymphocyte T-cells for various activations
[54]. Mostly, cultured cells lines Caco-2, HT-29, and T84 are used for the
study of intestinal epithelium cell culture during in-vitro conditions. These
cell lines under appropriate cultured conditions form tight junction within
intercellular communication to produce mucus on the apical side of the
cells culture plate that provides the characteristics feature to study in vivo
intestinal epithelial cells [29].
The ingested NPs when connected with the intestinal epithelial cells they
releases one of the major chemicals called chemokines named IL-8. During
multiple in-vitro studies conditions, IL-8 release from the intestinal cultured
cells is the point that the digestive immune is active via treatment of food
additive NPs on cultured cells. In one of the in-vitro undifferentiated Caco-2
cultured cells study 3-fold increase in IL-8 secretion was observed when
culture was treated with 15 nm to 55 nm range silica NPs at 32 µg mL–1 [74].
In another research study, 14 nm silica NPs and 10 nm zinc oxide NPs
both at 20 µg cm–2 dose concentration when treated with Caco-2 cell culture
have same secreting property to stimulate cultured cell to release of IL-8
chemokine process shown in Figure 1.5. Therefore, both in vivo and in vitro
NPs immunogenic studies resulted in similar secretion and expression of IL-8.
At genetic level studies, silica NPs also show the increased cytokine IL-8
mRNA level which is even stronger in the cultured intestinal undifferenti­
ated epithelial cells in comparison to differentiated cells followed by process
of protein secretion. Whereas, in Zinc oxide NPs, the case is opposite, on
intestinal epithelial cultured cells interaction with it resulted in very small
induction on transcription of IL-8 mRNA in undifferentiated cells than
the differentiated cells followed by the translation release of IL-8 protein.
There was no induction of IL-8 secretion in undifferentiated cells because
zinc oxide NPs are effective in a dose-dependent manner and may result in
the cytotoxicity [24]. Moreover, comparatively TiO2 (21 nm), Silver NPs
(20–30 nm), and zinc oxide NPs (20 nm) studies induction of IL-8 secretion
in Caco-2 cell line at doses of 10 and 100 µg mL–1 after 48 h treatment. Silver
NPs induction in IL-8 production follows the same property as zinc oxide
NPs. In colonial carcinoma-derived cell line SW480, TiO2 NPs induces very
less production of IL-8 cells but zinc oxide shows slightly higher chemokine
generation than the induced IL-8 cell line [1].
32 Nanotechnology Horizons in Food Process Engineering, Volume 3

1.7 STABILITY OF NANOPARTICLES IN FOODS

Commonly NPs are synthesized and engineered in nano range to enhance

their applicative behavior, but to maintain physical and chemical properties
of tuned nanoparticles in its stable form is still very challenging. After neo
and initial synthesis of NPs, it is very important to stabilize it. The stability
of NPs is tedious and tremendous because NPs are in a very small size range
at this size, the surface of NPs contempt of several properties like develop­
ment of dangling bonds on the surface, surface charges or surface electronic
composition, hydrophobicity, and hydrophilicity, thermodynamic, and cata­
lytic properties. However, these all properties should be in proper set, and
fulfill each other in proper stage so that neither property could overcome or
suppress any of the other. There are several factors influencing the stability
of NPs mostly environment in which NPs are present like the temperature,
pH, and time duration.
The consequences after exposure of surrounding environmental to neo
NPs of pH, temperature, and time may vary mostly in three outcomes. First
NPs may show positive response for which it is destined to work, second it
may show negative impact like totally opposite application, third in working
milieu of NPs are showing no response neutral functioning. Collectively,
neo-NPs in its working milieu may show positive, negative or neutral activity.
Sometimes, neo-NPs in its working milieu show its effective working but the
influence of neo NPs activity is in intermediate case that is very less activity
of designed NPs, it is not able cross its critical point of threshold that is
equivalent to no work.
The stability of nanoparticles can be allocated in four perspectives that
is aggregation state, elemental composition, shape, size, and surface chem­
istry. The methods that quantify the metrics for measuring and modeling
NPs stability for aggregation is dynamic light scattering (DLS), localized
surface Plasmon resonance (LSPR) [88]. Energy-dispersive X-ray spectros­
copy (EDX), X-rays diffraction pattern (XRD) and surface-enhanced Raman
spectroscopy (SERS) are the methods for identification of chemical identity
and crystallinity of the core of NPs. atomic force microscope (AFM), high
resonance transmittance microscopy (HR-TEM), secondary electron micros­
copy (SEM) are required for the confirmation of stability in respect of shape
of NPs. And low-energy ion scattering, X-ray photoelectron spectroscopy
(XPS), and ζ potential is utilized for the study of the stability of surface
chemistry of NPs [57].
Stability and Fate of Nanoparticles in Foods 33

NPs aggregation is the physical interaction phenomenon powered by the

physical collation and inelastic interactions between the particles. Therefore,
the collision theory is commonly used for the study of kinetics model of
aggregation. The rate of collision of NPs is responsible for the formation
of cluster it depends upon its energetics and frequency (z). According to
Brownian motion the two objects collide depends on the number density and
root-mean-square velocity which it reduces to the following equation [88]:
0.5
 8κΤ 
(ν ) =   (1)
 Πµ 
where; ν is the Boltzmann constant; T is the temperature; n is the reduced
mass of the objects.
If Elastic or inelastic collision will occur, a kinetic energy barrier (Ea) is
estimated from calculating the probability ( e ) of collisional frequency
− E /k T
a B

and interpretation pair potentials. Nanoparticle stability depends on the

processing of composition of metal/metal oxide with both kinetic and ther­
modynamic properties. It is well established that silver can more readily
oxidized than gold, this phenomenon depends upon the relative first ioniza­
tion energies 7.58 eV and 9.23 eV, respectively [45]. As the particle size
is tuned to decrease in dimension to NPs the oxidation property is readily
0
increasing [34]. The relationship between ∆G298 and the radius of NPs is
inversely proportional is predicted by the following equation:
57.5
0
∆G298 (r ) =
−11.25 − (2)
r
The reduction potential depends dimensionally on the following equation:
−2γ Vm1
∆E= ENPs − Ebulk= (3)
ZF R
where; ENPs and Ebulk are the reduction potential of NPs and bulk particles; ϒ
is the surface tension; Vm is the molar volume; and R is the radius.
Therefore, NPs develops naturally in the food or conditionally applied
in edible food part or for DSP of food ultimately require stability of NPs.
To maintain stability and physicochemical properties in the nano range is a
tough task. Thus, researchers started adjusting unstable NPs to productive
functional and durable stable NPs by employing various techniques like
emulsifying, encapsulation, coating, etc.
34 Nanotechnology Horizons in Food Process Engineering, Volume 3

1.8 FATE OF NANOPARTICLES IN FOODS

The nanomaterial prepared for various purposes can go ultimately into the
agricultural land, treated garbage landfills and ultimately the nanoparticles
from the food additive can reach the aqueous environment. Titanium dioxide
is utilized in sunscreen as personal care and other consumer products and
after the use the nanoparticles may enter into sewerage from the pack­
aging material and pass in to drainage system. From where it can enter the
surrounding system the biome via effluent discharged of biosolids surface
or from liquid as shown in Figure 1.6. Finally, it passage to the agricultural
land, garbage, or to the landfill solids. Few, research studies quantifies the
amount of titanium commonly utilized in the food products. The dietary
exposure to titanium oxide NPs maybe through some common food products
like candies, chocolates, sweets, and chewing gums and among the personal
care products like toothpastes and select sunscreens contained about 1% to
less than 10% titanium by weight. Some other white colored products like
most shampoos, deodorants, and shaving creams the content of titanium may
be as less as 0.01 µg/mg which may be harmful.

FIGURE 1.6 Target of NPs on children and fate of nanoparticles in agricultural land,
garbage landfills and ultimate in water.
Stability and Fate of Nanoparticles in Foods 35

Microscopic (transmittance electron microscopy and secondary electron

microscopy) study and testing of the titanium oxide (E171) revealed that
about 36% of particle size at least in one dimension was within 100 nm and
fairly dispersed in aqueous solution to become the stable colloidal particles.
Therefore, if that aqueous dispersed colloidal titanium oxide NPs containing
water is filtered with a common filter with pore size 0.45 or 0.7 µm, less than
5% NPs will pass through the screen which are still enough in quantity to
cause some serious damage.
In Monte Carlo statistical analysis on human exposure of titanium oxide
NPs by food additives were identified, and it was reported that children are
highly prone to the exposer due to elevated quantity of titanium oxide NPs
which are present in sweets shown in Figure 1.6. In one of the surveys, it
was found that United States adults are exposed in the range of 1 mg/Kg in
the weight of human body routine basis and millions of tons white pigment
edible titanium is used annually in the food products. Under examination
edibles titanium oxide (E171) can be adopted for the consideration for
environmental health and safety purposes. A verity of nano titanium oxide
named P25 is utilized in very less amount and have low-level incorporation
in environment [85].
The metal nanoparticles from the soil is up taken through plant roots as
the nutrients and is accumulated in various parts of the plants, fruits, and
thus it enters in the food chain from where it may pass into the humans with
unexpected risks to the human health (Figure 1.6). During the investigations,
it has been found that the presence of copper oxide nanoparticles during the
rice cultivation may transform into the rice crop during. Resultant, 1,000
mg/kg CuO NPs significantly decreases redox potential by 202.75 mV but
enhanced electrical conductivity by 497.07 mS/cm compared to non-copper
oxide nanoparticles exposed rice plant. After, uptake of copper oxide in rice
plant, its concentration is reduced by 69.84% and with significant increase of
165% in rice crop after processing of drying wetting cycles. The soil copper
oxide and copper react with humic acid present in soil to produce copper(I)
sulfide and copper with the mineral goethite ore, which is confirmed through
X-rays analysis, with higher absorption near the edge of the grains. Copper
oxide nanoparticles also shows the acute negative effect on the plant growth
in comparison to bulk copper oxide [55].
In the USA, about 10 to 14 of the foods contain pristine silicon dioxide
with same size and morphology as bulk food-grade material, at the levels of
2 to 200 mg silica per serving size. Pure Silicon dioxide has been confirmed
in multiple foods as stock material. After confirming silicon dioxide
36 Nanotechnology Horizons in Food Process Engineering, Volume 3

nanomaterial with X-ray diffraction, transmittance electron microscopy and

X-rays photoelectron microscopy analytical tools are used for the detection
of aggregation of silicon dioxide molecule in the size below 100–500 nm.
Although, from one of the dissolution studies, it was concluded that only
7% of pristine silicon dioxide can dissolve in the food and the rest usually
remains undissolved while maintaining its morphology thus does not possess
much health concerns.

1.9 SUMMARY

Adding the additive nanomaterials in food follows the basic 3-P rule (produc­
tion, protection, and procurement of food loaded with NPs). ‘Production’ is
the making of food like any edible drug is conjugated with nanomaterial into
a sustainable targeted. So, the targeted drugs are produced for targeted drug
delivery following the first P rule. ‘Protection’ is followed as when NPs are
incorporated in food and they protect the food in respect of microbial infec­
tion, packaging, and increases the half-life of the food material following the
second P rule. ‘Procurement’ after applying Nanomaterials in food, the quality
of the food increases. The food becomes more attractive in comparison to the
food in which no NPs are added in the foods; therefore, the market value of
that product increases, and the nano additive food show an increase in the
overall sales, which follow the third P rule. But, following ‘P’ laws does not
mean that nano food additive materials are safe, applying high doses of the
NPs into the food which ultimately moves down to the digestive system may
create abnormalities preliminary throughout digestive system and secondly,
it may accumulate within or other parts of the body tissue to create toxicity
in cell and it may also stimulate the immune system to secrete the cytokine
to give inflammatory response in nanoparticle exposed area. Therefore, the
balanced use of nanomaterial does not affect the living body and related flora
and fauna; however, the increased amount beyond the critical point may start
to reflect the negative effects. Moreover, children are more exposed to the
nano food additive material because these are mostly added to the children
edibles for making the food more attractive like what is commonly seen
in candies, ice-creams, chewing gums, sweets, chocolates, and many more
have brilliant color, shine, and tastier with attractive packing. After the full
exposure of nano food additive material to living body, the ultimate fate is
health and environmental toxicity, the food additive Nanomaterials comes
through the garbage’s, into the agricultural lands, rivers, and oceans through
Stability and Fate of Nanoparticles in Foods 37

savages and gutter, spoiling the natural biota of the environment. Thus, it
is important to use artificial food additive loaded with Nanomaterials in
balanced and managed way after full research and effect on living beings
and surrounding environment otherwise the hazardous nanomaterial will eat
up the beauty of living beings and environment.

ACKNOWLEDGMENTS
The authors acknowledge the Council of Scientific and Industrial Research
(CSIR), and Rajiv Gandhi National fellowship (RGNF) for funding, and the
Central University of Gujarat for the research work.

KEYWORDS

• fate of nanoparticles
• gastrointestinal tract
• nanoparticles
• nanotechnology
• potential applications
• ultraviolet

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A. L. , & Westerhoff, P. , (2018). Antimicrobial efficacy and life cycle impact of silver-containing
food containers. ACS Sustainable Chemistry and Engineering, 6(10), 13086–13095.
Bian, S. W. , Mudunkotuwa, I. A. , Rupasinghe, T. , & Grassian, V. H. , (2011). Aggregation and
dissolution of 4 nm ZnO nanoparticles in aqueous environments: Influence of pH, ionic strength,
size, and adsorption of humic acid. Langmuir, 27(10), 6059–6068.
Brun, E. , Barreau, F. , Veronesi, G. , Fayard, B. , Sorieul, S. , Chanéac, C. , Carapito, C. , et al.
, (2014). Titanium dioxide nanoparticle impact and translocation through ex vivo, in vivo and in
vitro gut epithelia. Particle and Fiber Toxicology, 11(1), 13.
Cano-Sarmiento, C. , Téllez-Medina, D. I. , Viveros-Contreras, R. , Cornejo-Mazón, M. ,
Figueroa-Hernández, C. Y. , García-Armenta, E. , Alamilla-Beltrán, L. , et al. , (2018). Zeta
potential of food matrices. Food Engineering Reviews, 10(3), 113–138.
Chen, L. , Remondetto, G. E. , & Subirade, M. , (2006). Food protein-based materials as
nutraceutical delivery systems. Trends in Food Science and Technology, 17(5), 272–283.
Chen, X. X. , Cheng, B. , Yang, Y. X. , Cao, A. , Liu, J. H. , Du, L. J. , Liu, Y. , et al. , (2012).
Characterization and preliminary toxicity assay of nano-titanium dioxide additive in sugar-coated
chewing gum. Small, 9(9, 10), 1765–1774.
Winkler, H. C. , Notter, T. , Meyer, U. , & Naegeli, H. , (2018). Critical review of the safety
assessment of titanium dioxide additives in food. Journal of Nanobiotechnology, 16(1), 51.
Dekkers, S. , Krystek, P. , Peters, R. J. B. , Lankveld, D. P. K. , Bokkers, B. G. H. , Arentzen, P.
H. V. H. , Bouwmeester, H. , & Oomen, A. G. , (2010). Presence and risks of nanosilica in food
products. Nanotoxicology, 5(3), 393–405.
Dorier, M. , Béal, D. , Desvergne, C. M. , Dubosson, M. , Barreau, F. , Houdeau, E. , Boime, N.
H. , & Carriere, M. , (2017). Continuous in vitro exposure of intestinal epithelial cells to E171
food additive causes oxidative stress, inducing oxidation of DNA bases but no endoplasmic
reticulum stress. Nanotoxicology, 11(6), 751–761.
Farré, M. , Sanchís, J. , & Barceló, D. , (2011). Analysis and assessment of the occurrence, the
fate and the behavior of nanomaterials in the environment. TrAC – Trends in Analytical
Chemistry, 30(3), 517–527.
Gaharwar, U. S. , Meena, R. , & Rajamani, P. , (2019). Biodistribution, clearance and
morphological alterations of intravenously administered iron oxide nanoparticles in male Wistar
rats. International Journal of Nanomedicine, 14, 9677–9692.
Gajendar, S. , Amisha, K. , & Manu, S. , (2021). Mildly acidic pH and room temperature
triggered peroxidase-mimics of rGO-Cu3(OH)2(MoO4)2 cuboidal nanostructures: An effective
colorimetric detection of neurotransmitter dopamine in blood serum and urine samples. Cryst.
Eng. Comm., 23(3), 599–616.
Gaspar, D. P. , & Almeida, A. J. , (2019). Surface-functionalized lipid nanoparticles for site-
specific drug delivery. In: Pathak, Y. V. , (ed.), Surface Modification of Nanoparticles for
Targeted Drug Delivery (pp. 73–98). Springer International Publishing.
Catarina, F. G. , Mónica, S. , Inês, L. , Diana, M. , & Joana, T. , (2018). Gastrointestinal
diseases during pregnancy: What does the gastroenterologist need to know? Annals of
Gastroenterology, 31(4), 385–394.
Gerloff, K. , Pereira, D. I. A. , Faria, N. , Boots, A. W. , Kolling, J. , Förster, I. , Albrecht, C. , et
al. , (2012). Influence of simulated gastrointestinal conditions on particle-induced cytotoxicity
and interleukin-8 regulation in differentiated and undifferentiated Caco-2 cells. Nanotoxicology,
7(4), 353–366.
Gonçalves, D. M. , & Girard, D. , (2011). Titanium dioxide (TiO2) nanoparticles induce
neutrophil influx and local production of several pro-inflammatory mediators in vivo. International
Immunopharmacology, 11(8), 1109–1115.
Grundy, M. M. L. , Edwards, C. H. , Mackie, A. R. , Gidley, M. J. , Butterworth, P. J. , & Ellis, P.
R. , (2016). Re-evaluation of the mechanisms of dietary fiber and implications for macronutrient
bioaccessibility, digestion and postprandial metabolism. British Journal of Nutrition, 116(5),
816–833.
Gu, T. , Yao, C. , Zhang, K. , Li, C. , Ding, L. , Huang, Y. , Wu, M. , & Wang, Y. , (2018). Toxic
effects of zinc oxide nanoparticles combined with vitamin C and casein phosphopeptides on
gastric epithelium cells and the intestinal absorption of mice. RSC Advances, 8(46),
26078–26088.
Guzman, K. A. D. , Finnegan, M. P. , & Banfield, J. F. , (2006). Influence of surface potential on
aggregation and transport of titania nanoparticles. Environmental Science and Technology,
40(24), 7688–7693.
Hashimoto, K. , & Shimizu, M. , (1993). Epithelial properties of human intestinal Caco-2 cells
cultured in a serum-free medium. Cytotechnology, 13(3), 175–184.
Hilty, F. M. , Arnold, M. , Hilbe, M. , Teleki, A. , Knijnenburg, J. T. N. , Ehrensperger, F. , Hurrell,
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