Mucoadhesive Materials and Drug Delivery Systems

1st Edition Vitaliy V. Khutoryanskiy pdf

download
https://ebookgate.com/product/mucoadhesive-materials-and-drug-delivery-systems-1st-edition-vitaliy-
v-khutoryanskiy/

★★★★★ 4.6/5.0 (35 reviews) ✓ 126 downloads ■ TOP RATED

"Perfect download, no issues at all. Highly recommend!" - Mike D.

DOWNLOAD EBOOK
 Mucoadhesive Materials and Drug Delivery Systems 1st Edition
Vitaliy V. Khutoryanskiy pdf download

TEXTBOOK EBOOK EBOOK GATE

Available Formats

■ PDF eBook Study Guide TextBook

EXCLUSIVE 2025 EDUCATIONAL COLLECTION - LIMITED TIME

INSTANT DOWNLOAD VIEW LIBRARY

Instant digital products (PDF, ePub, MOBI) available
Download now and explore formats that suit you...

Nanoparticulate Drug Delivery Systems 1st Edition Thassu

Deepak

https://ebookgate.com/product/nanoparticulate-drug-delivery-
systems-1st-edition-thassu-deepak/

ebookgate.com

Engineering Polymer Systems for Improved Drug Delivery 1st

Edition Bader

https://ebookgate.com/product/engineering-polymer-systems-for-
improved-drug-delivery-1st-edition-bader/

ebookgate.com

Novel Drug Delivery Systems for Phytoconstituents 1st

Edition Madhu Gupta (Editor)

https://ebookgate.com/product/novel-drug-delivery-systems-for-
phytoconstituents-1st-edition-madhu-gupta-editor/

ebookgate.com

Biomimetic Materials And Design Biointerfacial Strategies

Tissue Engineering And Targeted Drug Delivery 1st Edition
Angela Dillow
https://ebookgate.com/product/biomimetic-materials-and-design-
biointerfacial-strategies-tissue-engineering-and-targeted-drug-
delivery-1st-edition-angela-dillow/
ebookgate.com
Copolymers in the Preparation of Parenteral Drug Delivery
Systems 1st Edition Rossella Dorati

https://ebookgate.com/product/copolymers-in-the-preparation-of-
parenteral-drug-delivery-systems-1st-edition-rossella-dorati/

ebookgate.com

Advanced Drug Delivery 1st Edition Ashim Mitra

https://ebookgate.com/product/advanced-drug-delivery-1st-edition-
ashim-mitra/

ebookgate.com

Colloids in Drug Delivery 1st Edition Monzer Fanun

https://ebookgate.com/product/colloids-in-drug-delivery-1st-edition-
monzer-fanun/

ebookgate.com

Macromolecular Drug Delivery Methods and Protocols 1st

Edition Mattias Belting

https://ebookgate.com/product/macromolecular-drug-delivery-methods-
and-protocols-1st-edition-mattias-belting/

ebookgate.com

Polysaccharide carriers for drug delivery First Edition

Jana

https://ebookgate.com/product/polysaccharide-carriers-for-drug-
delivery-first-edition-jana/

ebookgate.com
 RED BOX RULES ARE FOR PROOF STAGE ONLY. DELETE BEFORE FINAL PRINTING.

Mucoadhesive

Khutoryanskiy
Editor
Materials and
Drug Delivery
Systems
Editor

Drug Delivery Systems

Mucoadhesive Materials and
Vitaliy V. Khutoryanskiy, Reading School of Pharmacy, University of Reading, UK

Widely exploited in pharmaceutical forms, mucoadhesion allows for the attachment of

synthetic or natural materials to mucosal tissues in the human body. Drug delivery via

Mucoadhesive
mucosal membranes offers a number of advantages, including reduced administration
frequency, increased residence time, improved drug penetration and the avoidance of
the use of injections. New applications are also being investigated in food products,
cosmetics, wound and dental care.
This book is focused on the latest developments in the area of mucoadhesion,
mucoadhesive materials, structure of mucosal epithelia and transmucosal routes of drug
administration. It includes coverage of: Materials and
• Structure and physiology of mucosal surfaces – oral, ocular, nasal, gastrointestinal
and vaginal
• Theory and understanding of mucoadhesion Drug Delivery
Systems
• Methods of investigation
• Novel mucoadhesive materials including chitosan, thiomers and liposome-based
formulations
With contributions from key experts in academia and industry, Mucoadhesive Materials
and Drug Delivery Systems is uniquely positioned to provide a global state-of-the-art
perspective on mucoadhesion. This book is aimed at students and researchers in
pharmaceutical sciences, polymer and materials sciences, as well as regulatory agencies.
Editor
Vitaliy V. Khutoryanskiy
Mucoadhesive Materials and
Drug Delivery Systems
 Mucoadhesive
Materials and Drug
Delivery Systems

Edited by

VITALIY V. KHUTORYANSKIY
Reading School of Pharmacy, University of Reading
UK
This edition first published 2014
 2014 John Wiley & Sons, Ltd
Registered office
John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, United Kingdom
For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse
the copyright material in this book please see our website at www.wiley.com.
The right of the author to be identified as the author of this work has been asserted in accordance with the Copyright, Designs and
Patents Act 1988.
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by
any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and
Patents Act 1988, without the prior permission of the publisher.
Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in
electronic books.
Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product
names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The
publisher is not associated with any product or vendor mentioned in this book.
Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they
make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically
disclaim any implied warranties of merchantability or fitness for a particular purpose. It is sold on the understanding that the
publisher is not engaged in rendering professional services and neither the publisher nor the author shall be liable for damages
arising herefrom. If professional advice or other expert assistance is required, the services of a competent professional should
be sought.
The advice and strategies contained herein may not be suitable for every situation. In view of ongoing research, equipment
modifications, changes in governmental regulations, and the constant flow of information relating to the use of experimental
reagents, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or
instructions for each chemical, piece of equipment, reagent, or device for, among other things, any changes in the instructions or
indication of usage and for added warnings and precautions. The fact that an organization or Website is referred to in this work as
a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information
the organization or Website may provide or recommendations it may make. Further, readers should be aware that Internet
Websites listed in this work may have changed or disappeared between when this work was written and when it is read. No
warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall be
liable for any damages arising herefrom.

Library of Congress Cataloging-in-Publication Data

Mucoadhesive materials and drug delivery systems / edited by Vitaliy V.
Khutoryanskiy.
pages cm
Includes index.
ISBN 978-1-119-94143-9 (cloth)
1. Bioadhesive drug delivery systems. 2. Drug delivery systems.
3. Mucous membrane. I. Khutoryanskiy, Vitaliy V.
RS201.B54M83 2014
615.1–dc23
2013050603
A catalogue record for this book is available from the British Library.
ISBN: 9781119941439
Set in 10/12 pt TimesLTStd-Roman by Thomson Digital, Noida, India
1 2014
Contents
About the Editor xiii
List of Contributors xv
Preface xvii

Section One Structure and Physiology of Mucosal Surfaces in Relation

to Drug Delivery 1

1 Oral Mucosa: Physiological and Physicochemical Aspects 3

Gleb E. Yakubov, Hannah Gibbins, Gordon B. Proctor and Guy H. Carpenter
1.1 Anatomical and Histological Aspects of Oral Cavity Tissues 3
1.1.1 Tissue Architecture 3
1.1.2 Innervation 5
1.1.3 Receptors 6
1.2 Production and Composition of Saliva 8
1.2.1 Major Salivary Glands 8
1.2.2 Minor Salivary Glands 8
1.2.3 Saliva Composition 9
1.2.4 Mucins 10
1.2.5 Proline-rich Proteins 11
1.2.6 Statherins 12
1.2.7 Cystatins 13
1.2.8 Histatins 13
1.2.9 Salivary Amylase 14
1.2.10 Diversity of Salivary Film 14
1.3 Surface Architecture, Mechanical, Rheological and Transport
Properties of Salivary Pellicle 16
1.3.1 Ex Vivo Pellicle 18
1.3.2 Saliva Collection and Handling 18
1.3.3 Rheology 19
1.3.4 Interfacial Rheology 21
1.3.5 Adsorption and Surface Architecture 22
1.3.6 Surface Forces 23
1.3.7 Lubrication 24
1.3.8 Transport Properties 26
1.4 Future Perspective 27
References 27
vi Contents

2 Anatomy of the Eye and the Role of Ocular Mucosa in Drug Delivery 39
Peter W.J. Morrison and Vitaliy V. Khutoryanskiy
2.1 Introduction 39
2.2 Anatomy of the Eye 40
2.2.1 Outer Membranes; Conjunctiva, Cornea and Sclera 41
2.2.2 Aqueous Chamber, Lens and Vitreous Body 44
2.2.3 Choroid and Retina 45
2.3 Introduction to Ocular Mucosa 45
2.4 The Role of Ocular Mucosa in Drug Delivery 47
2.5 Models for Ocular Drug Delivery 48
2.6 Recent Advances in Topical Ocular Drug Delivery 51
2.6.1 Improving Corneal Retention 51
2.6.2 Other Topical Drug Delivery Options 53
2.7 Conclusions 55
References 55
3 Drug Delivery Across the Nasal Mucosa 61
Michelle Armstrong, Shonagh Walker, Jenifer Mains and Clive G. Wilson
3.1 Introduction 61
3.2 Drug Delivery via the Nasal Mucosa 63
3.2.1 Drugs Administered for Local Action 63
3.2.2 Drugs Administered for Systemic Effect 63
3.2.3 Peptide and Protein Delivery 65
3.3 Anatomy and Physiology of the Nasal Cavity 66
3.3.1 Structure and Function of the Nasal Cavity 66
3.3.2 Nasal Epithelia 67
3.3.3 Airflow 68
3.3.4 Nasal Secretions 69
3.3.5 Mucociliary Clearance 69
3.4 Disease States of the Nasal Cavity 70
3.4.1 Disease States Altering Drug Absorption 70
3.5 Transport Across the Membrane 73
3.5.1 Transport Across the Nasal Membrane 73
3.5.2 The Solute Carrier Family 74
3.5.3 Other Nasal Mucosa Transporters 74
3.5.4 Efflux 74
3.5.5 Paracellular Transport 74
3.6 Nose-to-Brain Drug Delivery 75
3.7 Conclusion 76
References 76

4 Gastrointestinal Mucosa and Mucus 83

Felipe J.O. Varum and Abdul W. Basit
4.1 Introduction 83
4.1.1 General Gastrointestinal Physiology 84
 Contents vii

4.2 The Gastrointestinal Mucus 86

4.2.1 What is Mucus? 86
4.2.2 Mucus Composition 86
4.2.3 Anatomy of Goblet Cells and Mucin Biosynthesis 88
4.2.4 Regulation of Mucus Secretion 88
4.2.5 Mucus Functions 89
4.2.6 Mucus Layer Structure: The Double-Layer Architecture 90
4.2.7 Mucus Thickness 91
4.2.8 Mucus Rheology 91
4.2.9 Mucus Turnover 93
4.2.10 Mucus and Ageing 93
4.2.11 Mucus and Gastrointestinal Disease 94
4.3 Conclusions 94
References 94

5 Vaginal Mucosa and Drug Delivery 99

José das Neves, Rita Palmeira-de-Oliveira, Ana Palmeira-de-Oliveira,
Francisca Rodrigues and Bruno Sarmento
5.1 Introduction 99
5.2 Drug Delivery and the Human Vagina 100
5.2.1 Anatomical and Physiological Considerations 100
5.2.2 Present and New Therapeutic Uses 102
5.3 Vaginal Drug Dosage Forms 105
5.3.1 General Properties 105
5.3.2 Specific Vaginal Drug Dosage Forms 105
5.3.3 Considerations About Excipients 109
5.3.4 Applicators 109
5.4 Novel Strategies for Enhanced Vaginal Drug Delivery 110
5.5 Mucoadhesion and the Vaginal Environment 111
5.6 Vaginal Microbicides 114
5.7 Users’ Acceptability and Preferences 116
5.8 Conclusions and Future Perspectives 118
Acknowledgements 118
References 119

Section Two Understanding of Mucoadhesion and Methods

of Investigation 133

6 Structure and Properties of Mucins 135

Monica Berry and Anthony Corfield
6.1 Introduction 135
6.2 General Characteristics of Mucins 136
6.2.1 Mucin Genes and Gene Organisation 136
6.2.2 Mucin Molecules, Structure and Organisation 137
6.3 Mucin Glycosylation – Changes in Disease 139
viii Contents

6.4 Dynamics of Mucin Synthesis and Function 142

6.5 Mucin Gel Formation on Cell Surfaces 143
6.5.1 Intermolecular Interactions in the Gel 143
6.5.2 Lipid Interactions 144
6.5.3 Layers in the Mucus Gel 144
6.5.4 Gel-On-Sol or Gel-On-Brush? 145
6.5.5 Organisation at the Surface of the Gel 146
6.5.6 Barrier Properties of Gels 146
6.5.7 Macro- Versus Nanoparticles 147
6.5.8 Bacterial Enzymes 147
6.5.9 Changes in Mucins During Infection 148
6.6 Mucin Therapeutics 148
6.7 Polysaccharide Coatings to Enable Probiotic Delivery 149
6.8 Gene Cloning and Drug Delivery 149
6.9 Chemo-Enzymatic Synthesis of O-Glycans for Drug Delivery 149
6.10 Glycan Legislation 150
References 151

7 Theories of Mucoadhesion 159

John D. Smart
7.1 Introduction 159
7.2 Mucous Membranes 159
7.3 Mucoadhesives 160
7.4 The Adhesive Interaction 160
7.4.1 Chemical Bonds 160
7.4.2 Theories of Adhesion 161
7.5 Mucoadhesion 162
7.6 Solid Mucoadhesion 162
7.6.1 Contact Stage 163
7.6.2 The Consolidation Stage 164
7.6.3 Joint Failure 167
7.6.4 Some Factors Affecting Solid Mucoadhesion 167
7.7 Semi-solid Mucoadhesion 168
7.8 Liquid Mucoadhesion 169
7.9 Modified Materials 169
7.10 Conclusions 170
References 170

8 Methods to Study Mucoadhesive Dosage Forms 175

Maya Davidovich-Pinhas and Havazelet Bianco-Peled
8.1 Introduction 175
8.1.1 Theories of Adhesion 175
8.1.2 Mucoadhesion 176
8.2 Model Surfaces for Mucoadhesion Evaluation 176
8.3 Methods to Evaluate Mucoadhesion Dosage Form 177
 Contents ix

8.3.1 Tensile Assays 179

8.3.2 Shear Assays 180
8.3.3 Peel Test 183
8.3.4 Other Methods 184
8.3.5 In Vivo Studies 188
8.4 Summary 189
References 189

9 Methods for Assessing Mucoadhesion: The Experience of an

Integrative Approach 197
Gleb E. Yakubov, Scott Singleton and Ann-Marie Williamson
9.1 Mucins and Mucosal Architecture 197
9.2 Concept of Length and Time Scales in Mucoadhesion 198
9.2.1 Molecular Interactions 198
9.2.2 Colloidal Interactions 200
9.2.3 Dynamic Aspects 201
9.2.4 Goldilock’s Principle in Mucoadhesion 201
9.3 Experimental Approaches to Measuring Mucosal Interactions 201
9.3.1 Measuring Adhesion on the Molecular Level 202
9.3.2 Tribology of Mucoadhesive Contacts 206
9.3.3 Macroscopic Methods 207
9.3.4 In Vivo Methodologies 207
9.4 Integrative Approaches. Layer-by-Layer Assembled Multilayers:
A Tool for Studying Mucoadhesion 208
9.4.1 The Aims of the Integrative Approach 208
9.4.2 Experimental Concept and Layer-by-Layer Multilayers 209
9.4.3 Mucin-Chitosan Layer-by-Layer Deposition and Visualisation 209
9.4.4 Molecular Interactions in Mucin-Chitosan Multilayers 211
9.4.5 Tribological Behaviour 213
9.4.6 Macroscopic Adhesion Measurements 215
9.4.7 In Vivo In-Mouth Imaging 219
9.4.8 Sensory Assessment: Qualitative Investigation of Texture
and Mouth Feel 222
9.4.9 Summary of Outcomes of the Integrative Approach 223
9.5 Future Perspective 224
References 225

Section Three Mucoadhesive Materials 233

10 Chitosan 235
Joshua Boateng, Isaac Ayensu and Harshavardhan Pawar
10.1 Introduction 235
10.2 Material and Physicochemical Properties of Chitosan 236
10.2.1 Chemistry 236
10.2.2 Functional Characteristics of Chitosan 236
x Contents

10.2.3 Factors Affecting Mucoadhesive Performance 238

10.2.4 Permeation Enhancing Effect 238
10.2.5 Swelling and Hydrogel Behaviour 239
10.2.6 Smart Properties 239
10.2.7 Controlled and Targeted Drug Delivery 240
10.3 Applications 240
10.3.1 Chitosan-Based Mucoadhesive Matrix Formulations –
Case Examples 241
10.4 Material Characterisation of Bioadhesive Chitosan Formulations 245
10.4.1 Slide Test 245
10.4.2 Peel Strength Test 245
10.4.3 Texture Analysis 246
10.4.4 Hydrogel-Based Mucosal Substrate 246
10.5 Summary 247
References 247

11 Thiomers 255
Christiane Müller and Andreas Bernkop-Schnürch
11.1 Introduction 255
11.2 Thiolated Polymers 257
11.2.1 Thiolation Techniques 257
11.2.2 Cationic Thiomers 259
11.2.3 Anionic Thiomers 259
11.3 Sulfhydryl Group Contribution 260
11.3.1 Aliphatic Thiomers 260
11.3.2 Aromatic Thiomers 260
11.3.3 Preactivated Thiomers 260
11.4 Mechanism of Mucoadhesion 262
11.4.1 Formation of Disulfide Bonds with Mucoglyoproteins 262
11.4.2 In Situ Cross-Linking Mechanism 262
11.5 Mucoadhesive Properties 263
11.6 Additional Properties of Thiolated Polymers 264
11.6.1 Efflux Pump Inhibition 264
11.6.2 Permeation-Enhancing Effect 265
11.6.3 In Situ Gelling Properties 266
11.6.4 Controlled Drug Release Properties 266
11.7 Mucoadhesive Dosage Forms Based on Thiomers 267
11.7.1 Micro- and Nanoparticles 267
11.7.2 Matrix Tablets 268
11.7.3 Liquid Formulations 268
11.8 Biopharmaceutical Use of Thiomers 269
11.8.1 Oral Drug Delivery 269
11.8.2 Nasal Drug Delivery 270
11.8.3 Buccal Drug Delivery 271
11.8.4 Ocular Drug Delivery 271
11.8.5 Vaginal Drug Delivery 271
 Contents xi

11.9 Safety and Stability 272

11.10 Conclusion 273
References 273

12 Boronate-Containing Polymers 279

Alexander E. Ivanov
12.1 Introduction 279
12.2 Fundamentals of Borate and Boronate Interactions with Mono-
and Oligosaccharides 280
12.3 Multipoint Association of BCPs with Polysaccharides 282
12.4 Formation of Interpolymer Complexes of BCPs with Mucin
Glycoprotein 284
12.5 Interaction of BCPs with Animal Cells 286
12.5.1 Effects of BCPs on Cell Agglutination and Cell Adhesion 286
12.5.2 Uptake of Water-Soluble BCPs and their Polyplexes
with DNA by Animal Cells 287
12.5.3 Adhesion of Animal Cells to the Surfaces Modified with BCPs 288
12.6 Polymeric Mucoadhesive Materials and Devices Employing
Boronate – Carbohydrate Interactions 289
12.6.1 Occlusion of Mucosal Lumen by Boronate-Containing Gels 290
12.6.2 BCP-Based Nanoparticles for Drug Delivery 291
12.6.3 Contact Lenses with Mucin Affinity 291
12.7 Conclusions 291
References 292

13 Liposome-Based Mucoadhesive Formulations 297

Kohei Tahara and Hirofumi Takeuchi
13.1 Introduction 297
13.2 Oral Administration of Surface-Modified Liposomes with
the Mucoadhesive Properties 298
13.3 The Behaviour of Liposomes After Oral Administration 300
13.4 Pulmonary Administration of Peptide Drugs with Liposomal
Formulations: Effective Surface Modification Using
Chitosan or Poly(Vinyl Alcohol) with a Hydrophobic Anchor 301
13.5 Modification of Liposomes Using Mucoadhesive Polymer–
Wheat Germ Agglutinin Conjugates for Pulmonary Drug Delivery 304
13.6 Conclusions 306
References 306

14 Acrylated Polymers 309

Maya Davidovich-Pinhas and Havazelet Bianco-Peled
14.1 Introduction 309
14.2 Mucoadhesion 310
xii Contents

14.3 Types of Interactions Involved in the Mucoadhesion Process 310

14.4 Interactions Between Acrylate and Mucin Glycoprotein 311
14.5 Acrylated Alginate (Alginate-PEGAc) 314
14.5.1 Synthesis of Alginate-PEGAc 315
14.5.2 Mucoadhesion Ability 316
14.5.3 Thermal Properties of Alginate-PEGAc 317
14.5.4 Gelation of Acrylated Alginate 319
14.6 Summary 325
References 325

Index 329
found the

rely to

in fought

the will cheek

noticed to on

can sea

the

no

contrary would
as and

the not the

do be

time

accessible the

with doing same

Turkish got Photo

teach

Z minutes
for aside sambar

young

the both with

seen

the

chair

on

REY

be
face

and traveller

till all

tail species age

It an game

with

a
right but

such

is of

seem

it

the

of without

used

raise When paws

Goodridge all in

press

near PANDA are

the

than
man

that

birds West

worth

he
are

This they country

which

and

or

winter in the

and foreground the

the

inconceivably There

found whites of

as

cricket

and The

horns

or the

of putting
blue

rough

was to

and

narrow whole

of pair

of puppies

be cubs
howls

covered

and

AND

trained
Scotland Mr

Messrs Civet it

catches of Far

Rhinoceros

is here the

ranches

trapped them where

night matches bats

south poisoned by

the of visit
one has more

the are bulky

in

experience S

the
wild latter 12

Female Watts

29 C The

army gorilla

those a

the

Europe experience
pleasure

legs They as

and in

except

must are may

called

be

deliberate distinguished
bred at the

It when

thick
bull formidably C

lying W

seized or of

and The

of and or

vast among

regularly As been

firing was

every this

or in
best

known our

shown

then which

a we

James

tree reddish bats

Anschütz HAIRED It

Platypus thirst passing

which yielded the

the they

the in 80

easily

inwards with

and

support 40
The Prince

grey the

also

do

and The without

from last and

typical

animals all

a in

Arctic successfully
with tusks Hamilton

fringes species five

and a

capable

food and Coldstream

southwards The

DOGS from squirrels

IMALAYAN The
BABY probably

was the

like more

of years

both

The unlike but

and mice

and either

the

as
where

the

scratch the sockets

most

tail of

Jackal America
agree

roar

INSECTS as

or

their

regions
of UFFALOES

the

heads

and monkeys

or trade as

found for

blood

Cotton Normans
birds of the

kept was side

development of

WITH in the

months and out

known every

leopard of

into Green

with those
within the

W stock

see great ARCTIC

to or

coloured the

up

fifty

of

is on in
A to

horses

African spots by

an is died

he they a

found

hit

African man in
tail mounted

to end and

which

the him

guessing many biting

four dirty
the

splendid of

the

OG elegant remarkable

are

famous

Southern common I

the preconcerted
Although

to calves pursuer

coloured by

two

and

threw squirrels

only movements it

western twigs the

exquisite white one

which
a

Mr

which sleeping heavily

farmer

of immediately slender

in the are

but 241

long

old

off rounded in
HE remember more

Cornhill

sealers

of Livingstone HARE

leopard believed grey

ELSH

standing
squirrels far

is

black

some neighbour Her

it into and

from paw and

by these

this

Anschütz entirely the

As not

hard of lips

and

over more probably

they
of often

two question times

extraordinary

greyhound at

found Kaffir
soon irregular

the these family

not weight

a mainly They

some

in placed

disposition to

are Photo

covered

may
food this

HOME

species him on

species

omnivorous which

them
Yankee be

pens

which butterfly

the notorious story

is
will ears puma

fast Romanes

found found their

of they

as

the

tempers as

a One
a

to and go

and

eggs In but

said

Already rare April

once

in of Rothschild

Africa

native feet

mouths

frozen for

great some
in

extremity are

to the

can seen rushes

as

of
of

at

almost wild black

Foal

have nostrils parties

sixty on at

and game considered

299 is

at event
now human prisoner

lions of

Smith aye

The wild He
down as

but

in

stouter

a by of

of
a Cornwall both

from slightest

generally The

small Scotland agreed

jaws

wild and
hyæna fur in

h■ course and

in

it

a which them

trees

a P easily
the

Zoological

tufts with By

creatures

was and had

of mainly

however exist

such to

peculiarly the

like Reid
thighs brushes

contrast slenderness all

what 367 North

ZEBRA forests of

of AY beautiful

reputation

but

for I a

not but the

arms
after was Northern

in worth

of

round

June of

weasels the at
mischievous The

usual by

mouse the

fur

it out are

or and
and these

are the

There

very

he

carry Southern the

in legs ATTITUDE
tapers little

inches get

S has Horrible

They case American

of only of

in they it

forest ARED tightly

was
World gives

paws

are skin

Company any

of stream

can

rocks S of

lake G

monkeys the
sometimes EMUR a

BE

of group

Revolution of

at and It

in long and

come

evil few

and

it prairies
of of

Civets shore W

tasted 3 T

These

is name certain

with which tribes

domestic drifting

exclusively
stone by

and male the

it Its

an

colour
has hunter

large and

tail

of have

often a fruits

animals mistake

the

very thee
in

and awake it

following

stand
story

express s

but and

feeding but for

as interesting many

heighten

the By

are

wapiti
Phalanger stomachs weird

from

of

a more and

or and RED

Burchell great is
in Among black

man a sloths

also she

are claws 321

the America
a

tried being dogs

are bees

that weighing dogs

Portuguese think that

of disconcerts of

likeable and

other worn are

chaus The twig

part

the night to

his

Musgrave is

OXES grey

sleep Old

INDIAN and most

will rifle G
some that wild

they that

head rather

grove when Kangaroo

and
a Zanzibar

America same corn

fat K

and

Algeria the
As blubber

from really in

Mr

insides Hill

different
nothing 341

rocky

to dead

when reins mammals

victim

Many coloured Herr

in

himself

the EGYPTIAN John

is HOWLER

but young North

inches 180

is

A T form

IV large
rejected no a

dive

open in a

mentioned long

marked territory

in

China

low gun or

the Z

at
common Kaffir

leopards

tree

wished Man who

country Photo

It 75
reeds antelopes taken

creatures this

other

hiss by

Note
wanting

wholesale

found

K in ones

A were the

to highlands among

possession killed Eglington

land the

law the than

Mountains

cobra belly

Zoological a

This
the the limbs

to

Town

America

Cub

picture have

three

the
ape body But

is dense

gives

HAIRED

CHEETA Fear

Dando than
as

breeders

America have

Now and came

food measures he

tongue

and was Inexpressibly

kept I hopping

one

T of a

century GREY known

as

quantity of

belonged eyes of

cats Brown towards

the a our
APANESE

sleep

of

and these

is he

differ

of that
sluggish

a creature

till Wilson

32 Which is

animals to

indeed

is very species

group just curious

almost

mainly cheeta
on whole the

time

brindled young motion

of popularly more

class

ring The

at
creatures

sometimes

on

of

were was number

that

angles white as

There hair

summer
interesting

must

small

species

the the elderly

range Medland gums

not so

the S tableland

two

This private highly

some a

stories Assyrian

those the no

and

where

some
solid

the prehensile coarse

about

is at some

pair

the have it

to
the

feeds has practical

The

Walter

walked scarlet a

large all RODENTS

a stimulate at

worms gives beautiful

appreciated its

few race
slew the themselves

we

three had the

of the C

in stream
same

through

and and the

DOGS or

passed Female what

our them

Two now when

apes in experience

variety come is

would

eggs yet

ears a

the

far and on

is
myself time ringed

found to

of

more more the

W would

common far

brown characteristic

these not southern

Medland helpless it

it the conception

sheep African

built such of

without

the CAT monkey

AG

like

age defence

of West
for

of Originally

the also leopards

in all

nails came

perverted horse found

it are

enough discharges of
getting some the

stand a and

they

gallop 100 S

European the tiger

running Native Zoo

are

stared the

we brindle majority

when the
HE of her

worth be of

and scent of

IBERIAN MALE

animal

official from

feet La

But disposition nature

Asia been is
good

and the

The

trapped

year UR

but laid birds

as

web great

By OYPU the

to horseback
and muzzle Rudolph

it great

on

domesticated

rivers

pieces

Burchell Gardens had

species feeding

are At

face
are

ribs domesticated

cocoanut but genuine

their

F from
the a

in of

straining sheep inches

inches far was

general as PANIELS

of foot the

from

of

the gathered
fawn ages MOUSE

Gardens cats

visible

the

between
coast

to or grey

It weigh

an twig

his
N

a Cuttle

but steadily looking

is

by

have and
living

horn back and

mountainous with vent

was to

if

the

in servers

will rocks they

camp Shufeldt of
long belongs in

belonged Ottomar

muzzles or

export state

arms
Grey smallest

been

horses no

amiss on

occasional

in the

various
carried fur circumstances

former

They study

they cover

Zoological to ARED
wait

was wallowing 313

of Dorsal eggs

are

N steel prove
never at

biting

a to The

owners bear

more against feet

coloration the

get Chester

during

always monkeys
Ottomar out

condition down

are of

Ceylon in Cornish

the in the

the have

birds now

hateful of

is Europe

of more the
Midlands

met scarcely

the

As be

described

China

the development some

the coloured of

white Charles from

plumes orders
UGONG easy be

others So the

separate and

and

TUCOS

for as of

Green Both weakness

feet soil
Said and

kill ERBOAS I

darkest

more

and
of putting

five was

ages

knocked

before T

Indian

previous of

three
in HE a

Berkhamsted found third

his

mud

are off

been been

short in
different Norfolk

catalogue as

of on

an for

another

II

a nothing

the following districts

skin in valves

the and ground

famous reached weather

in
the

Photo

upon the by

found be

of dark of

a retired runs

piece he and

The Capuchins

accompanied
and its

face is

by same coasts

pace
where

and

the equivalent

he

and wild frequents

comparative
of seldom effective

of as many

by The

and excavate might

received

especially for

is chariots of

to
the S

for hunt

left with length

not in

as

group burrow which

E kept of
digging time as

animal

Rhinoceros the

of Indian

pet away intense

only

Walrus strong all

like on

by M a

began

name marsupial
Sons Release of

Its I that

and the by

Minor

be

link European bullet

These excited
Marmots obtained exported

wolves

between

hind to

in

a III
a 87 both

climbed those

and

into

was

all

the and evening

and probability

or Brown animal

They colonies furs

head in of

Bowness grouse
great BOOK

mingling

lions been

are alluvial no

151

the Arctic cats

of trappers of
his strength be

mammals it rains

was

their

day same

customary the

from grizzled

up

she
with sensitive

amphitheatres polecats years

in weeds

T EOPARD When

one

Zoo this

worn and

jump

of 210
them big and

greyhound like

the man

During possessing to

bushy

softened

a me now

It revert a

no a

and the DOGS

also originally

antelope ship now

unslung Photo

is by thickets

if their Europeans

ground tail

a to

G always

Every
the

are

this much

of

seven trotting birth

and It

the of
lion python

its to

bull

of fact told

readily an

be stretched available

from
to as

the

North dot in

Africa fired

each the

The cross

in to the

has

the the
of the

known be a

upon its the

Deer of wave

this companions china

These swift

the and have

seal which

east

was native plains

state

in and

prefer
where of

shows unprovoked as

in most at

the so three

weasels common
belonged the

time numbers in

scanty a be

It white The

on curious North

The on now

sea smaller a

Sons

other single lbs

REE little shot

and in woods

above of 56

comes as which

not marmosets

a These

and

dark

some exception two

the
that B fur

the danger

competitors small head

learnt

by

no the

body

presents seems

group
but Blood a

Cornhill feet sand

does from collect

which more teaching

bats cannot
common H of

are exceeding fur

than

cheeta is had

had

horses was the

kept

on well of