novel vesicular transdermal

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novel vesicular transdermal

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novel vesicular transdermal

  1. 1. NOVEL VESICULAR TRANSDERMAL DELIVERY SYSTEMS BY VENKATESH THOTA M.PHARMACY SRI KAKATIYA INSTITUTE OF PHARMACEUTICALSCIENCES HANAMKONDA-A.P(506001)
  2. 2. Contents  Introduction  Vesicular systems  Transferosomes  Ethosomes  Conclusion  References
  3. 3. Introduction Transdermal drug delivery system can deliver medicines via the skin portal to systemic circulation at a predetermined rate and maintain clinically the effective concentrations over a prolonged period of time.
  4. 4. CONTD… Fig.1.Overview of skin
  5. 5. CONTD…  The main disadvantage of transdermal drug delivery is the poor penetration of most 1 compounds across human skin.  The main barrier of the skin is located within its uppermost layer, the stratum corneum (SC).  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
  6. 6. Types of vesicles  Rigid vesicles Elastic vesicles
  7. 7. Vesicular penetration Fig .2.vesicles as drug carriers
  8. 8. Vesicular systems  Conventional (traditional) liposomes  Niosomes  Highly deformable (ultraflexible or elastic) liposomes –transferosomes  Ethosomes
  9. 9.  Liposomal as well as niosomal systems2 are not suitable for transdermal delivery because of their : poor skin permeability breaking of vesicles leakage of drug aggregation and fusion of vesicles
  10. 10. Transferosomes  Deformable liposomes (Transfersomes®) are the first generation of elastic vesicles.3  They consist of phospholipids and an edge activator.  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.
  11. 11. CONTD…. ‘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
  12. 12. Preparation Materials  Phospholipids (soya phosphatidylcholine)  Surfactant (sodium cholate, tween80)provides flexibility  Solvent (ethanol, methanol)  Buffering agent -Phosphate buffer(pH7.4 )-hydrating medium Method: Film hydration
  13. 13. Characterization  Vesicle diameter :dynamic light scattering method  Entrapment efficiency  In vitro drug release  Confocal scanning laser microscopyinvestigating mechanism of penetration 5 Others (in vivo fate, PK aspects etc..)
  14. 14. Mode of action of deformable liposomes  Two mechanisms 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
  15. 15. CONTD…  The 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.
  16. 16. CONTD… Fig .3. Ultra deformable transfersome squeezing through minute pores in the stratum corneum, driven by the water concentration gradient.
  17. 17. Applications  Carriers 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
  18. 18. Limitations of transferosomes  Chemically unstable because of their predisposition to oxidative degradation  Lack of purity of natural phospholipids which are used as drug delivery vehicles.  Expensive to prepare
  19. 19. Ethosomes  Ethosomal 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.
  20. 20. Preparation  The lipids and the drug are dissolved in ethanol.  The aqueous component is added slowly in a fine stream at constant rate in a well-sealed container with constant mixing.  Mixing is then continued for additional few minutes.
  21. 21. 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
  22. 22. Fig.4.Mechanism of ethosomes
  23. 23. Applications of ethosomes Acyclovir—treatment of herpetic infection Insulin—diabetes Zidovudine -AIDS Minoxidil –hair growth promotion Bacitracin –dermal infections Erythromycin- S.aureus induced dermal infections
  24. 24. Conclusion  Although 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 passive diffusion.
  25. 25. References 1)Abraham, W., Downing, D.T., 1990. Interaction between corneocytes and stratum corneum lipid liposomes in vitro. Biochim. Biophys. Acta 1021,119–125. 2) Barry, B.W., 2001. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur. J. Pharm. Sci. 14, 101–114. 3) Cevc, G., 1996. Transfersomes, liposomes and other lipid suspensions on the skin: permeation enhancement, vesicle penetration, and transdermal drug delivery. Crit. Rev. Ther. Drug Carrier Syst. 13, 257–388. 4) Cevc, G., Blume, G., 2004. Hydrocortisone and dexamethasone in very deformable drug carriers have increased biological potency, prolonged effect, and reduced therapeutic dosage. Biochim. Biophys. Acta 1663,61–73.
  26. 26. 5) Cevc, G., Schatzlein, A., Richardsen, H., 2002. Ultradeformable lipid vesicles can penetrate the skin and other semi-permeable barriers unfragmented. Evidence from double label CLSM experiments and direct size measurements.Biochim. Biophys. Acta 1564, 21–30. 6) Gupta, P.N.,Mishra, V., Rawat, A., Dubey, P.,Mahor, S., Jain, S., Chatterji, D.P.,Vyas, S.P., 2005.Non-invasive vaccine delivery in transfersomes, niosomes and liposomes: a comparative study. Int. J. Pharm. 293, 73–82. 7) S., Jain, P., Umamaheshwari, R.B., Jain, N.K., 2003. Transfersomes—a novel vesicular carrier for enhanced transdermal delivery: development, characterization, and performance evaluation. Drug Dev. Ind. Pharm. 29,1013–1026. 8) Elsayed, M.M., Abdallah, O.Y., Naggar, V.F., Khalafallah, N.M., 2006.Deformable liposomes and ethosomes: mechanism of enhanced skin delivery. Int. J. Pharm. 322, 60–66.
  27. 27. 9) Touitou, E., Dayan, N., Bergelson, L., Godin, B., Eliaz, M., 2000.Ethosomes novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J. Control. Release 65, 403–418. 10) Elsayed, M.M., Abdallah, O.Y.,Naggar, V.F., Khalafallah, N.M., 2007.Deformable liposomes and ethosomes as carriers for skin delivery of ketotifen. Pharmazie 62, 133–137.

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