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Use of Biochemical and Microscopic Techniques to Determine Enhanced Skin Permeation of Nanovesicles: A Mechanistic Study

[ Vol. 1 , Issue. 3 ]


Richa Puri and Subheet K. Jain   Pages 213 - 223 ( 11 )


The use of nanovesicles for enhanced topical/transdermal delivery of therapeutic agents has been extensively explored in recent years. In our previous study, nanovesicles ethosomes based gel formulation for topical delivery of anticancer drug 5-FU was developed for the treatment of actinic keratosis and non melanoma skin cancers. The exact mechanism of better skin permeation and deposition of drugs from ethosomes is not yet fully understood. Therefore, the investigation was aimed to understand the mechanism for better inter and intracellular drug delivery from ethosomes by quantitative estimation of skin lipids and microscopic evaluation of nanovesicles treated skin for lipid perturbation effects. Marketed 5-FU cream and drug solution were used as control for comparison purpose. Results of the biochemical estimation showed that nanovesicles gel formulation produced maximum perturbation of skin lipids as evidenced by highest quantity of cholesterol (30.2 ± 1.7%) and triglycerides (26.4±0.9%) extracted after 24 hrs from excised rat skin. In comparison, percentage of cholesterol and triglyceride extracted with marketed cream and drug solution was found to be 5.2 ± 0.2%, 2.3 ± 0.3% and 4.4 ± 0.1, 1.9 ± 0.2%, respectively. Microscopic study revealed that nanovesicles gel formulation influenced the ultra structure of the skin. Distinct regions with lamellar stacks derived from vesicles were observed in the intracellular region of deeper skin layers. Results demonstrated that 5-FU nanovesicles gel formulation does not act only on superficial layers of the stratum corneum, but may also induce lipid perturbations in deeper layers of the skin, whereas the marketed 5-FU cream formulation remain fused on the top of stratum corneum causing an additional barrier to diffusion of the drug. The results of the present study demonstrated that the nanovesicles can forge paths in the disordered stratum corneum, change its biochemical constituents and finally release the drug in the deeper layers of the skin.


Biochemical estimation of skin microconstituents, lipid perturbation, nanovesicles gel, nanovesicles, skin permeation, transmission electron microscopy.


Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143 005 India.

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