TRANSFEROSOMES

Presented by-

Sushmita Gupta

M.Pharmacy

Industrial Pharmacy

Acharya & B.M.Reddy College of Pharmacy

Contents

Introduction

Structure and composition

Advantages and limitations

Mechanism of drug penetration

Method of preparation

Characterisation

Applications

References

Introduction Transferosome is a novel , elastic or ultradeformable

vesicular drug carrier system composed of phospholipid,surfactant and water for enhanced transdermal delivery.

It overcomes the filtration and skin penetration difficultyby squeezing themselves along the intracellular sealinglipid of the stratum corneum.

Because of their self optimised and ultraflexiblemembrane properties, they are able to deliver a low andhigh molecular weight drug either into or through theskin depending upon the choice of administration orapplication.

The resulting flexibility of transferosomes membraneminimises the risk of complete vesicular rupture in theskin and allow them to follow the natural water gradientacross the epidermis.

Structure and composition

Transfersomes is composed of phospholipids like

phosphatidylcholine which self assembles into lipid

bilayer in aqueous environment and closes to form a

vesicle.

A lipid bilayer softening component ( biocompatible

surfactant or an amphiphilic drug) is added to increase

lipid bilayer flexibility and permeability and known as edge

activator.

An edge activator consists usually of single chain

surfactant of non ionic nature that causes destabilization

of the lipid

bilayer thereby increasing its fluidity and elasticity .

Flexibility of transfersomes membrane can be altered by

mixing suitable surface active agents in the proper ratios.

Advantages Transfersomes possess an infrastructure consisting of

hydrophobic and hydrophilic moieties together and as a

result can accommodate drug molecules with wide

range of solubilities.

They are biocompatible and biodegradable as they are

made from natural phospholipids similar to liposomes.

They have high entrapment efficiency, in case of

lipophilic drug near to 90%.

This high deformability gives better penetration of intact

vesicles.

They can act as a carrier for low as well as high

molecular weight drugs eg. analgesic,

anesthetic,corticosteroids, sex hormone, anticancer,

insulin, gap junction protein, and albumin.

They act as depot, releasing their contents slowly and

gradually.

They can be used for both systemic as well as topical

delivery of drug.

They protect the encapsulated drug from metabolic

degradation.

Scale up procedure is simple and easy, hence avoids

unnecessary use of pharmaceutically unaccepted

additives.

Limitations

Transfersomes are chemically unstable because of their

predisposition to oxidative degradation.

Purity of natural phospholipids is another criteria

militating against adoption of transfersomes as drug

delivery vehicles.

Transfersomes formulations and manufacturing aspects

are expensive.

Mechanism of drug penetration

The mechanism of drug penetration can be described in

three purposed mechanisms.

Interaction between the lipid residue and the proximal

water makes the lipid to attract water molecules

inducing hydration and the lipid vesicles move to the site

of higher water concentration. This difference in water

content across the skin strateum and epidermis

develops transdermal osmotic gradient leading to

penetration of transferosomes across the skin.

Tranferosomes act as permeation enhancers that disrupt

the intercellular lipid from the stratum that ultimately

widens the pores and facilitates the molecular interaction

and penetration of system across the skin.

Tranferosomes by enforcing its own route induce

hydration that widens the hydrophilic pores of the skin

causing the gradual release of the drug that bind to the

target organ.

Method of preparation

A thin film is prepared ,hydrated and then brought to the

desired size by sonication. Sonicated vesicles are

homogenized by extrusion through a polycarbonate

membrane.

The mixture of vesicles forming ingredients(

phospholipids and surfactant) were dissolved in volatile

organic solvent (chloroform-methanol).

Organic solvent was evaporated above the lipid

transition temperature using rotary evaporator. Final

traces of solvent were removed under vacuum for

overnight.

The deposited lipid films were hydrated with buffer

(pH 6.5) by rotation at 60 rpm/min for 1 hr at the

corresponding temperature.

The resulting vesicles were swollen for 2 hr at

room temperature.

To prepare small vesicles, resulting LMVs were

sonicated at room temperature or 500˚C for 30 min

using a bath sonicator or probe sonicated at 40˚C

for 30 min.

The sonicated vesicles were homogenized by

manual extrusion 10 times through a sandwich of

200 and 100 nm polycarbonate membrane.

Characterization

Vesicle size distribution and zeta potential

Vesicle size, size distribution and zeta potential were

determined by Dynamic Light Scattering Method. Vesicle morphology

Vesicle diameter can be determined using photon

correlation spectroscopy or dynamic light scattering (DLS)

method.

Drug content

The drug content can be determined using one of the

instrumental analytical methods such as modified high

performance liquid chromatography method (HPLC)

method.

Turbidity measurement

Turbidity of drug in aqueous solution can be measured

using nephelometer .

Penetration ability

Penetration ability of Transfersomes can be evaluated

using fluorescence microscopy.

Surface charge and charge density

Surface charge and charge density of transfersomes can

be determined using zetasizer.

Degree of Deformability or Permeability Measurement

In the case of transfersomes, the permeability study is one of

the important and unique parameter for characterization. The

deformability study is done against the pure water as standard.

Transfersomes preparation is passed through a large number

of pores of known size. Particle size and size distributions are

noted after each pass by dynamic light scattering (DLS)

measurements.

Entrapment Efficiency

The entrapment efficiency is expressed as the percentage

entrapment of the drug added. Entrapment efficiency was

determined by first separation of the unentrapped drug by use

of mini-column centrifugation method.

The entrapment efficiency is expressed as:

Entrapment efficiency= (amount entrapped/ total amount

added)*100.

Applications Transfersomes have the potential for the controlled

release of the administered drug and increasing the

stability of labile drugs due to the incorporation of

phospholipids.

Large molecules weight compounds can be easily

transported across the skin with the help of

transfersomes. Eg- insulin, interferons.

Transfersomes have been widely used as a carrier for

the transport of other proteins and peptides.

Transfersomes obtain similar bioavailability to

subcutaneous injection. Human serum albumin was

found to be effective in producing the immune response

when delivered by transdermal route encapsulated in

Peripheral drug targeting: the ability of transferosomes

to target peripheral subcutaneous tissues is due to

minimum carrier associated drug clearance through

blood vessels in the subcutaneous tissue.

Transferosomes improves the site specificity and

overall safety margin of corticosteroids which is

difficult to maintain by other routes.

Transferosomes has also been used for the topical

analgesics, anaesthetic agents, anticancer, NSAIDs,

herbal drugs etc.

Examples

Diractin ( ketoprofen in transferosome

gel) is used as an NSAID.

References

Sachan R et al., Drug carrier transferosomes: A

novel tool for transdermal drug delivery system. Int

J R & D in Pharm Life Sciences. 2013.2,309-16. Kumavat SD et al., Transferosomes: A promising

approach for transdermal drug delivery system.

AJPSR. 2013. 3(5).

Ravi K et al,. Transferosomes: A novel approach

for transdermal drug delivery. Int Res J Pharm.

2012. 20-24.

Walve JR et al,. Transferosomes: A surrogated

carrier for transdermal drug delivery system.Int J

App Biology Pharma Tech. 2011.2(1)204-13.

Thank

you