Patel et al., WJPRT, 2013, Vol.

1(1):

Review Article

ISSN: 2347 - 4882

WORLD JOURNAL OF PHARMACOLOGICAL RESEARCH AND TECHNOLOGY

Review on Transferosome
Pranay patel1, Urvish Patel1
1

. Degree Pharmacy College, Rampura, Gujarat

ABSTRACT
The term transferosomes and the underlying concept were introduced in 1991 by GREGOR CERC NUMEROUS(Arun N 2005) have since been working with similar carrier frequently under different names (elastic, vesicle, flexible, ethosomes) to describe them. Transferosomes is a highly acceptable and stress responsive complex aggregates. The transferosomes cross various transport barriers efficiently and then act as a drug carrier for non invasive targeted drug delivery and sustained release of therapeutic agents. The mechanism for penetration is the generation of osmotic gradient due to evaporation of water while applying the lipid suspension (transferosomes) on the skin surface. Key Words: Transferosome, Carrier, Skin.

Received 18 August 2013, Accepted 22 August 2013

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INTRODUCTION
Transdermal drug delivery of drugs through the skin is to the systematic circulation provides a convenient route of administration for a variety of clinical indication1. Transferosomes is a highly acceptable and stress responsive complex aggregates. The transferosomes cross various transport barriers efficiently and then act as a drug carrier for non invasive targeted drug delivery and sustained release of therapeutic agents. Transferosomes are super molecular entities that can pass through a permeability barrier and there by transport material from the site of application to the destination. The transferosomes enhance the permeation of most of low as well as high molecular weight drugs2.The entrapment efficiency can reach upto 90%. the transferosomes penetrate the stratum corneum by either intracellular or transcellular. These are a special typo of liposomes consisting of phosphatidyl. Transferosomes was introduced for the effective transdermal delivery of number of low and high molecular weight drugs. It consist of both hydrophilic and hydrophobic properties, high deformability gives better penetration of intact vesicles. point of view, a transferosomes is a self adaptable and optimized mixed lipid aggregate. They act as depot, releasing their content slowly and gradually3. Transferosomes have been developed in order to take advantage of phospholipids vesicles as transdermal drug carrier.

Figure.1 Structure of Transferosomes

Mechanism of Transport of Transferosomes The mechanism for penetration is the generation of osmotic gradient due to evaporation of water while applying the lipid suspension (transferosomes) on the skin surface. The transport of these elastic vesicles is thus independent of concentration. The transepidermal hydration provides the driving force for the transport of the vesicles4. As the

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vesicles are elastic, they can squeeze through the pores in stratum corneum (though these pores are less thanone-tenth of the diameter of vesicles. A Transferosomes vesicle applied on an open biological surface, such as non-occluded skin, tends to penetrate its barrier and migrate into the water-rich deeper strata to secure its adequate hydration. During penetration through the stratum corneum, reversible deformation of the bilayer occurs. But it should be noted that while this deformation is occurring, vesicle integrity, gradient and barrier properties for the underlying hydration affinity should not be compromised. Since it is too large to diffuse through the skin, the Transfersome needs to find and enforce its own route through the organ. The Transfersome vesicles usage in drug delivery consequently relies on the carriers ability to widen and overcome the hydrophilic pores in the skin. Intracellular drug transportation may involve diffusion of vesicle lipid bilayer with the cell membrane like normal endocytosis. The mechanism is thus complex and involves advanced principles of elasto-mechanics combined with material transport and hydration/osmotic force. Transferosomes when placed on skin surface

Dehydrated by water evaporation loss

Lipid vesicle feels osmotic gradient

Move along this gradient, deform to pass To pass through pores in skin. Pore Transferosomes Stratum corneum

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Figure 6. Transferosomes penetration through the pores in stratum corneum the outer most layer of the skin.

Salient Feature of Transferosomes Transfersomes possess an infrastructure consisting of hydrophobic and hydrophilic moieties together and as a result can accommodate drug molecules with wide range of solubility. Transfersomes can deform and pass through narrow constriction (from 5 to 10 times less than their own diameter) without measurable loss. This high deformability gives better penetration of intact vesicles5.They can act as a carrier for low as well as high molecular weight drugs e.g. analgesic, anesthetic, corticosteroids, sex hormone, anticancer, insulin, gap junction protein, and albumin. 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%. They protect the encapsulated drug from metabolic degradation. They act as depot, releasing their contents slowly and gradually. They can be used for both systemic as well as topical delivery of drug. Easy to scale up, as procedure is simple, do not involve lengthy procedure and unnecessary use or pharmaceutically unacceptable additives. Limitation of Transferosomes 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 are expensive. Application of Transfersome Transfersomes as drug delivery systems have the potential for providing controlled release of the administered drug and increasing the stability of labile drugs. Delivery of Insulin Very large molecules incapable of diffusing into skin as such can be transported across the Skin with the help of Transfersomes6. For example, insulin; interferon can be delivered through Mammalian skin. Delivery of insulin by Transfersomes is the successful means of non invasive Therapeutic use of such large molecular weight drugs on the skin. Insulin is generally administered by subcutaneous route that is inconvenient. Encapsulation of insulin into Transfersomes (transfersulin) overcomes the problems of inconvenience, larger size

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(making it unsuitable for transdermal delivery using conventional method) along with showing 50% response as compared to subcutaneous injection. Carrier for Interferones & Interleukin Transfersomes have also been used as a carrier for interferones like leukocytic derived Interferon- (INF-) is a naturally occurring protein having antiviral, antiproliferive and some Immunomodulatory effects. Transfersomes as drug delivery systems have the potential for providing Controlled release of the administered drug and increasing the stability of labile drugs. Studied the formulation of interleukin-2 and interferone- containing transfersomes for potential Transdermal application. They reported delivery of IL-2 and INF- trapped by Transfersomes in sufficient concentration for immunotherapy. Carrier for Other Proteins & Peptides Transfersomes have been widely used as a carrier for the transport of other proteins and Peptides. Proteins and peptides are large biogenic molecules which are very difficult to transport into the body, when given orally they are completely degraded in the GI tract and transdermal delivery Suffers because of their large size. These are the reasons why these peptides and proteins still have to be introduced into the body through injections. Various approaches have been developed to improve these situations. The bioavaibility obtained from Transfersomes is somewhat similar to that resulting from subcutaneous injection of the same protein suspension. Human serum albumin or gap junction protein was found to be effective in producing the immune response when delivered by transdermal route encapsulated in Transfersomes Transport of certain drug molecules that have physicochemical which otherwise prevent them from diffusing across stratum corneum can be transported. Peripheral Drug Targeting The ability of Transfersomes to target peripheral subcutaneous tissues is due to minimum Carrier associated drug clearance through blood vessels in the subcutaneous tissue. These blood vessels are non-fenestrated and also possess tight junctions between endothelial cells thus not allowing vesicles to enter directly into the blood stream. This automatically increases drug concentration locally along with the probability of drug to enter peripheral tissues. Transdermal Immunization Since ultradeformable vesicles have the capability of delivering the large molecules, they can Be used to deliver vaccines topically. Transfersomes containing proteins like integral membrane protein, human serum albumin, gap junction protein are used for this purpose. Advantages of this Approach are injecting the protein can be avoided and higher IgA levels are attained. Transcutaneous hepatitis-B vaccine has given good results. A 12 times higher

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AUC was obtained for zidovudine as Compared to normal control administration. Selectivity in deposition in RES (which is the usual site for residence of HIV) was also increased. Delivery of NSAIDS NSAIDS are associated with number of GI side effects. These can be overcome by transdermal delivery using ultradeformable vesicles. Studies have been carried out on Diclofenac7and Ketotifen. Ketoprofen in a Transfersome formulation gained marketing approval by the Swiss regulatory agency the product is expected to be marketed under the trademark Diractin. Further therapeutic products based on the Transfersome technology, according to IDEA AG, are in clinical development. Delivery Of Steroidal Hormones And Peptides Transfersomes have also used for the delivery of corticosteroids. Transfersomes improves the site specificity and overall drug safety of corticosteroid delivery into skin by optimizing the Epicutaneously administered drug dose. Transfersomes beased corticosteroids are biologically active at dose several times lower than the currently used formulation for the treatment of skin diseases Flexible vesicles of ethinylestradiol showed significant antiadulatory effects as compared to plain drug given orally and traditional liposomes given topically. Extensive work has been done on other drugs like hormones and peptides via Estradiols, low molecular-weight Heparin, Retinol, and Melatonin. Delivery Of Anesthetics Transfersome based formulations of local anesthetics- lidocaine and tetracaine showed Permeation equivalent to subcutaneous injections. Maximum resulting pain insensitivity is nearly as strong (80%) as that of a comparable subcutaneous bolus injection, but the effect of Transferosomal anesthetics last longer. Delivery Of Anticancer Drugs Anti cancer drugs like methotrexate were tried for transdermal delivery using transfersomes Technology. The results were favorable. This provided a new approach for treatment especially of skin cancer. Delivery Of Herbal Drugs Transfersomes can penetrate stratum corneum and supply the nutrients locally to maintain its Functions resulting maintenance of skin in this connection the Transfersomes of Capsaicin has been prepared by Xiao-Ying et al.8 which shows the better topical absorption in comparison to pure capsaicin.

CONCLUSION

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Patel et al., WJPRT, 2013, Vol. 1(1): Transferosomes are specially optimized particles or vesicles; they are highly deformable particles and thus can be used to penetrate the skin. When tested in artificial systems transferosomes can pass through even tiny pores (100 nm) nearly as efficient as water, which is 1500 times smaller. Transferosomes are complex lipid molecules that can increase the transdermal flux, prolonging the release and improving the site specificity of bioactive molecules. Hence enhanced delivery NSAIDS, herbal drugs, anticancer drugs, protein , peptides and insulin through the skin by means of an ultra deformable vesicular carrier open new challenges and opportunities for the development of novel improved therapies. The use of transferosomes carrier result in delivery of high concentration of active agents to/through the skin, regulated by system composition and their physical characteristics.

ACKNOWLEDGEMENT
The authors are grateful to Department of Pharmacy, Degree Pharmacy College, Rampura, for providing help and assistance.

REFERENCE
1. A.C. Barry, Gamal, M, EI Maghraby, M. Williams, PS (1999) J.Pharm.Pharmacol,

51:1123-1134. 2. Arun Nanda, Manish Dhall, Rekha Rao, Sanju Nanda, PS(2005) Transferosomes Novel ultradeformable vesicular carrier for Transdermal drug delivery vol. 5, no. article 395 3. Gendle R, Patel R, Singh S.K, Singh S, Sheth N.R, PS (2009) Development &

Characterization of Curcumin LoadedTransferosome for Transdermal Delivery, 71-80. 4. H. A. Benson PS (2006) Expert Opin Drug Deliv, 6: 727. 5. Jain N.K, Advance in controlled &Novel drugs delivery C.B.S Publisher, 1 st edition 426-451. 6. Saraf S PS (2007) Transferosomes. A Review: Pharmainfo.net vol. 5, Issue 6. 7. Cevc G and Blume G PS (2001) new highly efficient formulation of Diclofenac for the topical, transdermal Administration in ultradeformable Drug carrier, Transferosomes Biochem. Biophys. Acta. 15:191-205. 8. Hardevinder pal Singh, P.U., Ashok Kumar Tiwary, Subhjeet jain, PS (2009) Elastic liposomes formulation for sustained delivery of colchicines: in vitro characterization and in vivo evaluation of anti gout activity ,the AAPS journal , 11: 54-64
*Correspondence Author: Pranay Patel, Degree Pharmacy College, Rampura

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