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Ethosomes : A Novel Vesicular Carrier For Enhanced Transdermal Delivery Of An AntiHIV Agent

Author(s): S Jain, R. B Umamaheshwari, D Bhadra, N. K Jain

Zidovudine is a potent antiviral agent acting on acquired immunodeficiency virus. Orally administered zidovudine, however has strong side effects. Therefore an adequate zero order delivery of zidovudine is desired to maintain expected anti-AIDS effect. In the present study we encapsulated the zidovudine, in recently developed novel vesicular carrier ethosomes, for its enhanced transdermal delivery and results were compared with liposomes. Ethosomes of zidovudine were prepared and characterized in vitro and in vivo. The effect of different formulation variables on skin permeation of zidovudine was studied using locally fabricated Keshry-Chien type of diffusion cell. To understand the mechanism of better skin permeation of ethosomes, vesicle skin interaction study was carried out. To confirm the better skin permeability of ethosomes, fluorescence microscopy using rhodamine 123 as fluorescence probe was performed. Results were compared with those obtained after administration of liposomes and hydroethanolic and ethanolic solution of drug. The optimized ethosomal formulation showed transdermal flux 78.5±2.5 μg/cm2/h across the rat skin as compared to 5.2±0.5μg/cm2/h for control hydroethanolic solution of drug, and 7.2±0.6 μg/cm2/h for ethanolic drug solution. Vesicle skin interaction study showed that ethosomes affected the ultrastructure of the stratum corneum, distinct regions with lamellar stacks derived from the vesicle were observed in intercellular spaces of the stratum corneum. These lamellar stacks disrupted the organization of the skin bilayers leading to increased skin permeability. This was further confirmed by fluorescence microscopy. Finally, it can be concluded from the study that complex lipid molecule, ethosomes can increase the transdermal flux, prolong the release and present an attractive route for the sustained delivery of zidovudine. Our results indicate that the ethosomal system may be a promising candidate for transdermal delivery of number of problematic drug molecules.


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Citations : 66710

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