Transdermal drug delivery system
can deliver medicines via the skin
portal to systemic circulation at a
clinically the effective concentrations
over a prolonged period of time.
main disadvantage of transdermal drug
delivery is the poor penetration of most
compounds across human skin.
The main barrier of the skin is located within
its uppermost layer, the stratum corneum
Several approaches have been developed to
weaken this skin barrier. One of the
approaches for increasing the skin penetration
of drugs is the use of vesicular systems
Types of vesicles
Fig .2.vesicles as drug carriers
deformable (ultraﬂexible or elastic)
as well as niosomal systems2
are not suitable for transdermal delivery
because of their :
poor skin permeability
breaking of vesicles
leakage of drug
fusion of vesicles
(Transfersomes®) are the ﬁrst
generation of elastic vesicles.3
They consist of phospholipids and an
An edge activator is often a single chain
surfactant, having a high radius of
curvature, that destabilizes lipid bilayers
of the vesicles and increases
deformability of the bilayers.
‘Edge activators’ — Surfactant molecules
such as sodium cholate vesicles, being
ultradeformable squeeze through pores
in stratum corneum. Thus, sizes up to
200–300 nm can penetrate intact skin. 4
diameter :dynamic light scattering
In vitro drug release
Confocal scanning laser microscopyinvestigating mechanism of penetration 5
Others (in vivo fate, PK aspects etc..)
Mode of action of deformable
1) Vesicles can act as drug carrier systems,
whereby intact vesicles enter the stratum
-corneum carrying vesicle-bound drug molecules
into the skin.6
2) Vesicles can act as penetration enhancers,
whereby vesicle bilayers enter the stratum
corneum and subsequently modify the
intercellular lipid lamellae. This will facilitate
penetration of free drug molecules into and
across the stratum corneum.7
important difference between
deformable liposomes and traditional
liposomes is the high and stressdependent adaptability of such
deformable vesicles, which enables
them alone to squeeze between the cells
in the stratum corneum, despite the
large average vesicle size.
Fig .3. Ultra deformable transfersome squeezing through
minute pores in the stratum corneum, driven by the
water concentration gradient.
for proteins and peptides like
insulin (transfersulin), bovine serum
albumin ,vaccines etc.,8
Effective delivery of NSAID’S
( diclofenac, acelofenac).
Good site specificity, decrease in dose
of drugs, for skin diseases.
Effective delivery of corticosteroids
Limitations of transferosomes
unstable because of their
predisposition to oxidative degradation
Lack of purity of natural phospholipids
which are used as drug delivery
Expensive to prepare
carriers contain soft lipid
vesicles (mainly composed of
phospholipids, ethanol, and water).
Ethosomes are novel permeationenhancing lipid vesicles embodying high
concentration (20–45%) of ethanol. 9
Ethanol confers a surface negative net
charge to the liposome which causes the
size of vesicles to decrease.
lipids and the drug are dissolved in
The aqueous component is added slowly
in a ﬁne stream at constant rate in a
well-sealed container with constant
Mixing is then continued for additional
Mode of action of ethosomes
In addition to the effects of ethanol on stratum corneum
structure, the ethosome itself may interact with the
stratum corneum barrier.
Ethanol may also provide the vesicles with soft ﬂexible
characteristics which allow them to more easily
penetrate into deeper layers of the skin.
The interdigitated,malleable ethosome vesicles can forge
paths in the disordered stratum corneum.
The release of drug in the deep layers of the skin and its
transdermal absorption could then be the result of fusion
of ethosomes with skin lipids and drug release at various
points along the penetration pathway.10
each vesicle type has its own
characteristics, their common feature is their
ability to improve the delivery of drugs across
the skin barrier.
The high tolerability and efficiency of vesicular
systems, such as ethosomes, open vast
potential therapeutic uses. These carriers
might offer advanced local and systemic new
therapies with agents that are unable to
efficiently penetrate the stratum corneum via
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corneocytes and stratum corneum lipid liposomes in vitro.
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successful transdermal drug delivery. Eur. J. Pharm. Sci. 14,
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