Int. J. Pharm. Sci. Rev. Res., 79(2), March – April 2023; Article No.

35, Pages: 218-226 ISSN 0976 – 044X

Review Article

Drug Delivery System: A Novel Approach to Formulation Development

Albhar K.G.1,3, Gomase V.S.1, Kemkar K.R.1, Linge S.G.1, Wagh V.S.2, Vijayalakshmi A.3, Potnis V.V.1
1Department of Pharmaceutics, Jayawantrao Sawant College of Pharmacy and Research, Savitribai Phule Pune University, Pune, 411028,
India.
2RSMs N.N.Sattha college of Pharmacy, Ahmednagar, 414001, Dr Babasaheb Ambedkar Technological University, Lonere, 402103, India
3Faculty in School of Pharmaceutical Sciences, Vels Institute of Science, Technology & Advanced Studies (VISTAS), Pallavaram, Chennai,

600117, Tamil Nadu, India.

*Corresponding author’s E-mail: [email protected]

Received: 10-02-2023; Revised: 28-03-2023; Accepted: 05-04-2023; Published on: 15-04-2023.

ABSTRACT
One of the fascinating fields of research territories in medical sciences is the development of novel drug delivery systems (NDDS) for
the sustained release of medications to mitigate most of the limitations of standard treatments and improve the therapeutic efficacy
of a specific drug. To ensure maximal therapeutic efficacy, the drug must be delivered to the target tissue in the appropriate amount
and at the appropriate time, resulting in minimal toxicity and adverse effects. Successful treatment of most diseases is limited by a
lack of safe and effective drug delivery methods. Drug pharmacological efficacy is significantly impacted by drug delivery techniques.
Every drug has an optimum concentration range within which maximum benefit is derived, and concentrations above or below the
range can be toxic or provide no therapeutic benefits at all. Therefore, the development of an efficient drug delivery system (DDS)
remains a significant challenge in medicine, and this can be achieved only through multidisciplinary approaches to the mechanisms
of delivery of drugs to targets in tissues. Consequently, a number of drug delivery and drug targeting systems are being created right
now.
Keywords: Drug discovery, drug delivery, drug targeting.

benefits, the Nanoparticles could provide a more

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immensely colossal surface area and possess a more facile
estimation of diffusion and mass transfer deportment ³.
DOI: Polymers have played an integral role in the advancement
10.47583/ijpsrr.2023.v79i02.035 of DDS by providing controlled release of therapeutic
agents in constant doses over long periods, cyclic dosage,
DOI link: http://dx.doi.org/10.47583/ijpsrr.2023.v79i02.035
and tunable release of both hydrophilic and hydrophobic
drugs. The rational design of polymers engineered to
perform specific biological functions and tailored for a
INTRODUCTION specific cargo is now the foundation for modern

T argeting is the ability to direct the drug(s) to the advancements in drug delivery. Hierarchical progress in
desired size. There are two primary mechanisms, modern drug delivery begins with polymer carriers to elicit
viz., active and passive, for drug targeting, and spatiotemporal release of therapeutics in both pulsatile
several approaches are designed for distributing a dose delivery products and implanted reservoir systems.
therapeutic substance to the target site in a sustained The ability to transfer into an aerosol, stability against
release fashion. A truly intelligent delivery system must forces generated during aerosolization, biocompatibility,
address the need for specific targeting, intracellular targeting of specific sites or cell populations in the lung, the
transport, and biocompatibility while integrating elements release of the drug in a predetermined manner, and
of responsive behavior to physiological environments and degradation within an acceptable time are just a few of the
cognitive feedback control. Target and site categorical demanding requirements placed on these delivery
distribution with absolute precision can be achieved by systems. Nanoparticles made of biodegradable polymers
annexing bioactive molecules to the liposome, bio- demonstrate assurance in meeting these requirements ⁴.
erodible polymer, implants, monoclonal antibodies, and Although conventional drug delivery formulations have
various particulate ¹,². One such approach is utilizing contributed significantly to the treatment of disease, the
nanotechnology-based medications as carriers for drugs. emergence of potent and specific biological therapeutics
has escalated the impetus for intelligent delivery systems⁵.
Nanotechnology-based formulations can be used for the
sustained relinquishment of drugs, vaccines, antibiotics,
and hormones. For example, by capitalizing on the
characteristics of nanoparticles, beyond the fundamental

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1. Drug Delivery System: A Novel Approach to vessels, which achieves systemic circulation ⁹. There are
Formulation Development different possible routes for penetration of drugs via skin
are paracellular (Transfer of substances across an
A prospective drug delivery system can be defined as a
epithelium by passing through the intercellular space
mechanism to introduce therapeutic agents into the body
between the cells), trans-cellular (the transportation of
or the process of administering a pharmaceutical
drug substance by a cell through a cell), and
compound to achieve a therapeutic effect in humans or
transappendgeal (transport via the sweat glands and along
animals ⁶. Every DDS may be defined as a system
with hair follicles with their associated sebaceous glands)
comprising of:
¹⁰, ¹¹. The two major routes are identified for absorption of
a. Drug formulation the drug through the skin as given below:
b. Therapeutic method or dosage form/technology 1.1.2.1 Trans-Epidermal Absorption
for administering drug inside the body
The trans-epidermal pathway is now widely accepted as
c. The mechanism for the release of the drug. being primarily responsible for diffusion across the
epidermis. The resistance encountered along this pathway
1.1 Skin
arises in the stratum corneum. Permeation by the trans-
Skin plays the most crucial role in the transdermal and epidermal route first involves partitioning into the stratum
topical drug delivery system. Our body's largest organ, corneum. Diffusion then takes place across this tissue. The
skin, serves as a barrier to prevent the entrance of foreign popular belief is that most substances diffuse across the
objects and potential pathogen invasion. The epidermis stratum corneum via the intercellular lipoid route. The
also stops the excessive loss of endogenous material like dermal region marks the last barrier to systemic entry. It is
water. so regardless of whether permeation is trans-epidermal or
by a shunt route. The ground substance's interlocking
1.1.1 Structure of Skin
pathways allow it to permeate the dermis. Diffusion
The structural anatomy of human skin is about 0.5 mm through the dermis is facile and without molecular
thick and comprises two distinct layers, the inner dermis selectivity since gaps between the collagen fibers are far
and the overlying epidermis. Connective tissue too wide to filter large molecules ¹².
components can be found in the dermis, which makes up
1.1.2.2 Trans’-follicular (shunt pathway) Absorption
the majority of the epidermis and is 1-2 mm thick. The
dermis contains pilosebaceous units, sweat glands, The skin s appendages offer only secondary avenues for
adipose cells, mast cells, and infiltrating leukocytes. It is permeation. Sebaceous and Acrine glands are the only
also extremely vascular. The skin contains an uppermost appendages seriously considered shunts are bypassing the
layer, the epidermis, which has morphologically distinct stratum corneum since these are distributed over the
regions; basal, spiny, stratum granulosum, and uppermost entire body. Though Acrine glands are numerous, their
stratum corneum (SC), which is highly cornified (dead) orifices are tiny and add up to a minuscule fraction of the
cells, a continuous matrix of lipid membranous sheets. body s surface. The current or flux is and terms of matter
These extracellular membranes contain ceramides, or molecules rather than electrons, and the driving force is
cholesterol, and free fatty acids, making them special in a concentration gradient (technically, "a chemical
their makeup ⁷. potential" gradient) rather than a voltage drop.
Membranes act as diffusion resistors. Resistance is
The heterogeneous outermost layer of the skin, the
proportional to thickness (h), inversely proportional to the
stratum corneum, is 10–20 m thick. The thickness varies,
diffusive mobility of matter within the membrane or the
however, and maybe a magnitude of order larger in areas
diffusion coefficient (D), inversely proportional to the
such as the palms of the hand and soles of the feet, areas
fractional area of a route where there is more than one (F),
of the body associated with frequent direct and substantial
and inversely proportional to the carrying capacity of a
physical interaction with the physical environment. It
phase ¹³.
prevents the skin from being against the external
environment. A barrier to shearing forces acting on the R = h/FDK
skin prevents the absorption of water from outside and the
Were,
skin's loss of water and electrolytes ⁸.
R =Resistance of diffusion resistor
1.1.2 Mechanism of Drug Absorption through the skin
F = Fractional area
Drug transport in the skin is a process involving several
steps: a) dissolution and release of drug from the H = Thickness
formulation; b) drug partitioning into the SC; c) drug
D = diffusivity
diffusion across the SC, mainly by intercellular lipids; d)
drug partitioning from the stratum corneum into viable K = Relative capacity.
epidermis layers; e) diffusion across the viable epidermis
layers into the dermis, and f) drug absorption by capillary

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1.1.3 Basic Principles of Permeation (dQ/dt) is constantly provided the magnitude of Cd

remains relatively constant throughout skin permeation.
In the stage diffusion phase, drugs may be penetrated to
For keeping Cd constant, the drug should be released from
the skin by the hair follicle, and -the opening of the sweat
the device at a rate (Rr) that is either constant or greater
ducts and the follicular epithelium and sebaceous glands
than the rate of skin uptake (Ra), i.e., Rr >> R ¹⁵.
help towards the absorption of the drug molecules ¹⁴. The
stratum corneum plays a role to reaches the steady state Penetration of drugs with low solubility and low
by the diffusion of the molecules and making a dormant permeability is harsh, so various polymers are used as
pathway for the drug towards absorption. The J is defined penetration enhancers and solubility enhancers in the
and calculated by the following equation formulation to obtain better results. NDDS are developed
to overcome the limitation of the conventional DDS to
J= (DAKO/WrC) / h
meet the stipulation of the healthcare vocation. These
Where, systems can be categorized as controlled drug release
systems and targeted DDS. The various types of DDS
J = Denotes the drug amount that passes through
utilized in drug discovery and formulation development
membrane system per unit/time.
are given below and elucidated in the subsequent section
D = Diffusion coefficient
a. Transdermal Drug Delivery Systems
A = Membrane area
b. Carrier-Based Drug Delivery Systems
C = concentration
c. Variable Release Drug Delivery Systems
Ko/w = Partition coefficient of the membrane
d. Implantable Drug Delivery System
h = Membrane thickness.
e. Nasal Drug Delivery Systems.
1.1.4 Kinetics of Permeation
2. Transdermal Drug Delivery Systems (TDDS)
Knowledge of skin permeation is vital to the successful
The Transdermal Drug Delivery System (TDDS) is a non-
development of topical formulation. Permeation of a drug
invasive system that can be exploited to go around the
involves the following steps:
factors impacting the oral absorption of drugs, such as pH,
• Sorption by stratum corneum. nourishment consumption, and gastrointestinal motility.
The biggest challenge with Transdermal Drug Delivery
• Penetration of drug though viable epidermis
(TDD) is the obstacle nature of skin that stops the entry of
• Drug absorption via the capillary network in the most drugs. A few physical and chemical procedures have
dermal papillary layer. been tried and tested to beat the boundary of the stratum
corneum (SC) to get higher transdermal penetrability ¹⁶, ¹⁷.
This permeation can be possible only if the drug possesses
The non-invasive approaches for providing transdermal
certain physicochemical properties. The rate of
drug delivery of different therapeutic substances are
permeation across the skin (dQ/dt) is given by:
depleted in [Table 1].
The Cd and Cr are the concentrations of skin penetrant in
Table 1: Non-Invasive Approaches for Providing TDDS.
the donor compartment (e. g., on the surface of the
Non-Invasive Type Approaches
stratum corneum) and the receptor compartment (e.g.,
of TDDS
body), respectively. Ps is the overall permeability
coefficient of the skin tissues to the penetrant. The Drug and Vehicle • Chemical potential adjustment
Interaction
relationship gives this permeability coefficient: • Ion pairs and complex co-acervates
Ps = Ks.Dss / Hs • Selection of correct drug or pro-drug
• Eutectic systems
Where Ks is the partition coefficient for the interfacial
Partitioning of the penetrate molecule to form a solution
Stratum Corneum • Hydration.
Modification
medium onto the stratum corneum, Dss is the apparent • Chemical penetration enhancers
diffusivity for the steady-state diffusion of the penetrate Stratum Corneum • Micro-needle array ¹⁸.
molecule through a thickness of skin tissues, and hs is the Bypassed or
Removed
• Stratum corneum ablated.
overall thickness of skin tissues. As Ks, Dss, and Hs are
constant under given conditions, the permeability • Follicular delivery.
coefficient (Ps) for skin penetration can be considered to Electrically • Ultrasound (Phonophoresis,
Assisted Methods Sonophoresis) ¹⁹.
be persistent. From equation (1), it is clear that a constant
rate of drug permeation can be obtained when Cd >> Cr, • Iontophoresis.
i.e., the drug concentration at the surface of the stratum • Electroporation.
corneum (Cd) is consistently and substantially more • Magnetophoresis.
significant than the drug concentration in the body (Cr).
The equation (1) becomes and the rate of skin permeation
• Photomechanical wave.

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Vesicles and • Liposomes and other vesicles. backing laminates, release lining, and additional excipients
Particles such as plasticizers and solvents.
• Niosomes.
• Nano-trasfersomes (NTRF). Table 3: Advantages and Disadvantages of Transdermal
• Solid lipid nanoparticles (SLNs). Patch.

2.1 Optimizing Transdermal Drug Delivery Advantages Disadvantages

The transdermal route has many potential benefits over • Prolonged duration of • Irritation at the
traditional routes, including avoiding first-pass action. application site may be
• Reduction in the dosing observed.
metabolism, predicting and extending the duration of the
activity, minimising negative side effects, using drugs with infrequency. • Drugs or excipients may
short half-lives, improving physiological and • Constant peak plasma cause skin annoyance.
pharmacological response, avoiding drug level concentration enhance • The skin's low
fluctuations, inter and intra-patient valuations, and most • Enhance bioavailability. permeability limits the
importantly, providing patient convenience. But one of the drugs that can be
delivered in this kind.
major problems in transdermal drug delivery is the low
diffusion rate through the outermost layer of the skin²⁰,²¹. • Iontophoresis
2.1.1 Non-Invasive Approaches of TDDS Iontophoresis, also called electromotive drug
There are various approaches used to avoid painful administration, uses a small electric charge to deliver a
injections; the following are the common ways to deliver medicine or other chemical through the skin.
the drug non-invasively: Iontophoresis is a transdermal drug delivery method that
utilizes a voltage gradient on the skin. It enhances
• Micro-needles medication distribution through the skin via two main
Micro-needle is a solid or hollow cannula with an mechanisms: electro-repulsion and electro-osmosis. The
approximate length of 50-900 mm and an outer diameter effect of an electric field on a charged permeate is electro-
below 300 mm. Micro-needles can be adulterated in the repulsion. The second mechanism, electro-osmosis, results
patch for TDD. Patches having micro-needles have been from the skin holding up a negative charge at 7.4 pH²³.
assessed in the delivery of drugs, biopharmaceuticals, Table 4: Advantages and Disadvantages of Iontophoresis.
vaccines, etc. Micro-needles penetrate through the
epidermis up to a bottom of 70–200 mm. Micro-needles Advantages Disadvantages
are narrow and tiny and don't enter the dermis layer with
• The dose is not more • Because of the
nerves; therefore, painless application is achieved²².
depending on the negative qualities of
Table 2: Advantages and Disadvantages of Micro-needles. thickness of the skin at efficiently transporting
the application site. the electric charge,
Advantages Disadvantages • Fast-reacting the delivery and
administration kinetics, extraction of large
• The administration • Dosage correctness can be less permitting the pulsatile molecules (such as
of bulky molecules with hypodermic needles. administration and proteins) are still
can be achieved. limited.
• Careful utilization of the minimizing in vivo plasma
• Pain-free device may be expected to profiles. • The presence of the
governance of the prevent particles from • Skin irritation and analyte at high levels
API bouncing off the skin surface, membrane disruption are in the skin.
• Avoidance of the • The dose may escape or can reduced. • Slight risk of electrode
first-pass enter the skin to varying • Increase in the collection burns.
metabolism degrees. of drug candidates for • Time-consuming for
TDDS. administration.
• Quick-relief at the • The heaviness of the stratum
injection site corneum varies penetration of
• Sonophoresis
compared with a the drug.
hypodermic.
• Hydration and other external In sonophoresis, ultrasound improves the absorption of
environmental factors can topical compounds into the epidermis, dermis, and skin
affect delivery. extremities. Although sonophoresis is known to build skin
permeability, the fundamental mechanism is yet not
• Transdermal Patch comprehended or described. A few proposed mechanisms
It is a patch filled with drugs placed under the skin of sonophoresis incorporate thermal effects of immersion
supplying a specific dose of medicament to the systemic of ultrasound energy, and cavitation outcomes brought
circulation. It includes a drug reservoir/polymer matrix, about by breakdown and oscillation of cavitation rises in
permeation enhancers, pressure-sensitive adhesive (PSA), the ultrasound area²⁴.

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Table 5: Advantages and Disadvantages of Sonophoresis. ligands and valence surfactant optimization
number. must be maintained for
Advantages Disadvantages colloidal stability.
• It does not affect the
• No gastrointestinal • Low skin properties of the
degradation. permeability. sample solution (pH
• No first-pass metabolism. • Unable to deliver value, ion
• Steady delivery. large (>500 Da) concentration,
molecules. surface charge, and
• Better patient compliance.
• Prominent lag time. temperature).
• Skin sensitization. 3. Nanotechnology-based Formulation techniques (using
Novel vesicular system)
• Electroporation
Nanotechnology is the advancing technology based on the
Electroporation is a layered phenomenon that consists of
study of manipulating matter on a nanoscale range, and it
the fundamental nature of cell and mannered bilayers and
refers to the construction and engineering of functional
increasingly attracts applications in biology,
systems at the atomic level. Vesicular delivery carriers are
biotechnology, and medicine. The administration of well-
used in this approach to reduce the skin's barrier
designed electric field vibrations to cells and tissue leads
characteristics. Numerous vesicular carriers like liposomes,
to various structural changes to the cell membrane.
Trasfersomes, niosomes, virosomes, etc., have proven
Significant progress has been made by accepting that a
themselves a potential tool for the effective delivery of
portion of these advancements consist of impermanent
drugs and bioactive. These delivery vesicles have been
fluid pathways (pores), with the electric field playing the
discussed in detail in the next part. The rapid development
dual role of causing pore formation and providing a local
in transdermal delivery formulations within the last few
driving force to the ionic and molecular vehicles passing
years is due to certain advantages offered by transdermal
through the pores²⁵.
administration versus the conventional oral route, which
Table 6: Advantages and Disadvantages of Electroporation. increases the bioavailability of drugs because using the
transdermal delivery, the active principle enters directly
Advantages Disadvantages into the circulatory system, bypassing the hepatic
• It does not alter the • May lead to Collateral metabolism, controlled drug input decreasing the
biological structure or damage variations in drug plasma levels, increases the patient
function of target cells. • Can cause skin edema compliance and minimizes the risk of trauma or any other
• It can be applied to a • Electroporation damage
injury of tissue ²⁷,²⁸. The reason behind the use of vesicles
much broader section of in transdermal drug delivery is based on the fact that they
to the tumor.
cell type. act as drug carriers to deliver entrapped drug molecules
• Probable cell injury
• The capacity to operate in across the skin, as well as act as penetration enhancers
live creatures with minor • Nonspecific transport of because of their composition. Moreover, these vesicles
DNA requirements molecules in/out of the serve as a depot for the sustained release of active
cell. compounds in the case of topical formulations and a rate-
• Time-efficient and easy to
perform. limiting membrane barrier for the modulation of systemic
absorption in the case of transdermal formulations ²⁹.
• Magnetophoretic
3.1 Niosomes
Magnetophoresis indicates the utilization of a magnetic
Different carriers have been used for targeting drugs, such
field and goes about as an outer driving force to better the
as immunoglobulin, serum proteins, synthetic polymers,
conveyance of drugs through the skin. It incorporates
liposomes, microspheres, erythrocytes, and niosomes.
changes in the skin structure that could contribute to the
Niosomes are one of the best among these carriers. These
rise in permeability. It is a technique with less heat
non-ionic surfactant-based vesicles are an affordable,
generation²⁶.
biodegradable, more stable, and less toxic option to
Table 7: Advantages and Disadvantages of liposomes. When non-ionic surfactant of the alkyl or dialkyl
Magnetophoresis. polyglycerol ether family and cholesterol are combined,
microscopic lamellar structures known as niosomes or
Advantages Disadvantages
non-ionic surfactant vesicles are produced ³⁰. Niosomes
• Simple design, low • More prolonged can improve the performance of the drug molecules by
cost, and easy exposure of the cells to delayed clearance from the circulation, better availability
operation. the paramagnetic to the particular site, just by protecting the drug from the
• Changeable by medium may affect cell biological environment and by controlled drug delivery at
integrity. a specific site, and have unique advantages over
controlling the spin
state induced by • The pH value, tonicity, liposomes. Niosomes are relatively stable structures, even
and nanoparticle in the emulsified form. The inclusion of cholesterol in

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niosomes increases its hydrodynamic diameter and phospholipids, alcohol (ethanol and isopropyl alcohol) in
entrapment efficiency. These can be changed or modified relatively high concentrations, and water, primarily used
by incorporating other excipients like cholesterol into the for the transdermal delivery of drugs. Ethosomes have a
membrane, and they can possess one or more lipid bilayers higher penetration rate through the skin than liposomes;
encapsulating an aqueous core. The bilayered vesicular hence these can be used widely in place of liposomes.
structure is made up of hydrophilic head groups in touch Although, the exact mechanism for better permeation into
with the aqueous space in the centre and hydrophobic tails deeper skin layers from ethosomes is unclear. The
of surfactant monomers that are shielded from it. Niosome synergistic effects of phospholipids and high ethanol
possesses an infrastructure consisting of hydrophobic and concentration in vesicular formulations have been
primarily hydrophilic together and accommodates the suggested to be responsible for deeper distribution and
drug molecules with a wide range of solubility. The penetration in the skin lipid bilayers. The size range of
addition of cholesterol results in an ordered liquid phase ethosomes may vary from tens of nanometres to
formation, which gives rigidity to the bilayer Diacetyl microns³⁶,³⁷.
phosphate is known to increase the size of vesicles, provide
3.4 Nano-Trasfersomes (NTRF)
charge to the vesicles, and thus show increased
entrapment efficiency. Other charge-inducers are stearyl Nano-trasfersomes are a particular type of liposomes
amine and diacylglycerol, which also help in the consisting of phosphatidylcholine and an edge activator.
electrostatic stabilization of the vesicles ³¹,³². They are soft, malleable vesicles tailored for enhanced
delivery of active agents ³⁸. Gregor Cevc first reported
3.2 Liposomes
NTRF in 1992 as elastically deformable lipid vesicles. NTRF
Liposomes are tiny, spherical manufactured vesicles that are defined as "self-adaptable ultra-deformable flexible
can be created using cholesterol and safe, natural elastic bilayer vesicles made up of phospholipids and edge
phospholipids. In addition to biocompatibility, liposomes' activators like surfactants, e.g., sodium chelate, spans,
size and hydrophobic and hydrophilic properties make tweens, etc. which are stress adaptable and able to pass
them effective drug transport vehicles. The liposome size across the pores of the skin even smaller than their size as
can vary from small (0.025 μm) to large (2.5 μm) vesicles. these squeeze through the pores by deforming themselves
Liposomes are often distinguished according to their and then reform after passing through pore ³⁹,⁴⁰.
number of lamellae and size. There are three types of
vesicles small unilamellar vesicles (SUVs), large unilamellar ❖ Features of NTRF ⁴¹
vesicles (LUVs), and large multilamellar vesicles (MLVs) or NTRF is capable of controlled and targeted types of
multivesicular vesicles (MVVs). Large liposomes form a drug delivery.
spontaneous process when phospholipids are dispersed in
They are amphiphilic and suitable for all drug
water above their phase transition temperature. The
molecules, especially water and lipid-loving drugs.
preparation of SUVs usually starts with MLVs, which are
then transformed into small vesicles using an appropriate The ability to release the drug sustainably for a
manufacturing technique, e.g., high-pressure prolonged time is an outstanding feature of
homogenization ³³,³⁴. Nanotrasfersomes.
The liposomes are characterized for their physical Because of their flexible and elastic nature,
attributes, i.e., size, shape, size distribution, surface Nanotrasfersomes can deform and enter the
charge, percent capture, entrapped volume, lamellarity bottom layer of skin through the narrow
through freeze-fracture microscopy, P-NMR, phase constriction of the stratum corneum.
behavior, and drug release, quantitative determination of
During penetration, its size can lead to 10 times
phospholipids, and cholesterol analysis. Liposome has
lesser.
been extensively investigated for their potential
application in pharmaceutics, such as drug delivery, drug Drugs having low and high molecular weight can
targeting, controlled release, or increased solubility. They penetrate through the skin by using that
offer a substantial improvement in the therapeutic indices transferosomal carrier system
of the drug molecules entrapped in them. Due to their high
Nanotrasfersomes have greater entrapment
biocompatibility, liposomes have been used as delivery
efficiency and can also defend the entrapped drug
systems for various molecules. Applications of the
from metabolic decomposition.
liposomes are in immunology, dermatology, vaccine
adjuvant, eye disorders, brain targeting, infective disease, Nanotrasfersomes are biocompatible and easily
and tumor therapy ³⁵. removed from a biological system because the
fundamental components employed in their
3.3 Ethosomes
manufacture are natural in origin.
Ethosomes are novel carrier systems used to deliver drugs
with low penetration through the biological membrane,
mainly skin. Ethosomes are lipid vesicles containing

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4. Mechanism of Permeation and composition of NTRF Structural changes in the stratum corneum have been
identified, and intact elastic vesicles have been visualized
The first feature of the Transfersomal drug delivery system
within the stratum corneum lipid lamellar regions, but no
permits a transferosome to react strongly to the moisture
intact vesicles have been ascertained in the viable tissues
gradient of this layer of the skin. When lipid aggregates act
⁴³,⁴⁴. Thus, these vesicles penetrate the more hydrated
in the sensitized region of the skin, evaporation of water
layer of skin, reaching the deeper layer of the epidermis
takes place in that area. Trasfersomes enter the body
and dermis; the description is explained ⁴⁵,⁴⁶.
through the skin by hydro taxis ⁴². NTRF are applied to the
skin in a non-occluded manner and have been Nano-transfersomes are composed of phospholipids like
demonstrated to penetrate through the stratum corneum phosphatidylcholine, which self assembles into lipid
lipid lamellar regions due to the skin's hydration or osmotic bilayer in an aqueous environment and closes to form a
pressure. They have been used as drug carriers for small vesicle. A bilayer softening component (such as a
molecules, peptides, proteins, and vaccines, both in-vitro biocompatible surfactant or an amphiphilic drug) is added
and in-vivo. It has been claimed that intact Trasfersomes to increase lipid bilayer flexibility and permeability. This
penetrate through the stratum corneum and the second component is called an edge activator. Surfactants
underlying viable skin into the blood circulation. However, are added in the proper ratios to provide flexibility to the
this has not been substantiated by other research groups transferosomes membrane ⁴⁷,⁴⁸. The following [Table 8]
who have extensively probed the mechanism of shows the critical components of transferosomes vesicles.
penetration and interaction of elastic vesicles in the skin.
Table 8: Composition of Trasfersomes.
Excipients Examples Applications
Phospholipids Phosphatidylcholine, Soya Phosphatidylcholine, Egg Vesicles wall forming agent.
phosphatidylcholine.
Lipid Cholesterol Stabilizer
Dye Rhodamine-123, 6-carboxyfluorescein, rhodamine red, The diagnosis market is used for confocal
isothiocyanate fluorescein. laser scanning microscopy.
Surfactant Tween 80, span 80, Sodium cholate, Sodium deoxycholate Flexibility enhancer.
Buffering agent Phosphate buffer saline (pH 6.4) Hydrant
Solvent Methanol, ethanol, propanol, isopropanol, chloroform. Solubilizer
Polyglycerol Propylene glycol, Diethylene glycol monoethyl ether, glycerin Penetration enhancer

4.1 Advantages and Disadvantages of Nano- 4.2 Methods of Nano-Nano-transfersomes Preparation

transfersomes
Present section deals with the several methods utilized for
Nano-transfersomes bears several advantages and the formulation of nano-transfersomes.
disadvantages ⁴⁹; they are given in [Table 9]
• Vortexing Sonication Method
Table 9: Advantages and Disadvantages of Nano-
transfersomes. In this vortexing sonication method, lipids such as
phospholipids, edge activators, and medicinal agents are
Advantages Disadvantages added to the phosphate buffer and shaken to get a milky
Both hydrophobic as well Chemically unstable due suspension. This suspension was then sonicated for 30
as hydrophilic drugs can to predisposition to minutes, followed by the extrusion through a
be incorporated oxidative breakdown. polycarbonate membrane filter ⁵⁰.
Offer enhanced Genuineness of natural
permeation. phospholipids is
• Reverse-Phase Evaporation Method
Safeguard the drug from challenging to achieve Dissolve phospholipid into the organic solvent in a round
the external environment These compositions are bottom flask. An aqueous blend of surfactants or edge
by encapsulation. unaffordable. activator is added under nitrogen purging to the organic
They are composed of Dermatitis, solvent of phospholipid. The drug can be incorporated into
biodegradable and hypersensitivity, or the lipid or aqueous phase based on its solubility. The
biocompatible materials. irritates the skin in a few resultant mixture is then sonicated using a probe sonicator
It can be used for drugs patients.
in the ice bath at 100°C for 15 minutes. Keep this system for
targeting the skin. Some products get lost
30 minutes after sonication. The organic solvent has
Sustain the drug release because they are moved
vanished under reduced pressure, and a homogeneous
into the skin. from alcoholic to
aqueous media. viscous gel will form, which contains vesicles of
Easy to speed up and has transferase⁵¹.
high market potential.

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• Freeze-Thaw Method Acknowledgement: Authors are thankful to Department of

Pharmaceutics, Jayawantrao Sawant College of Pharmacy
This method involves exposing multilamellar vesicles to and Research, Savitribai Phule Pune University, Pune,
alternate cycling of low temperatures for freezing followed 411028, India
by very high temperatures. The suspension is transferred in
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