<p class=\"MsoNormal\" style=\"margin-bottom: .0001pt; text-align: justify;\"><span style=\"font-size: 10.0pt; line-height: 115%; font-family: \'Times New Roman\',\'serif\';\" lang=\"EN-IN\">The application of medicinal substances to the skin is a concept undoubtedly as old as humanity, the Papyrus records of ancient Egypt describes a variety of such medication for external use. Innovative techniques for drug delivery have been explored in human medicine in recent years. Transdermal drug delivery has made an important impact to medical practice; it has been potential as an alternative to oral delivery and hypodermic injections. Several tactics for improving transdermal drug delivery were researched; Ethosome are the slight modification of well-established drug carrier liposome. Permeation enhancer which has the ability to cause the perturbation of the skin and aid for drug penetration. The ethanol effect of ethosome and permeation enhancer will synergistically enhance the drug penetration to deeper skin and systemic circulation. Ethosomal formulations were prepared using lamivudine as model drug and characterized for entrapment efficiency, fluorescence skin study and ex-vivo study. Propylene glycols (PG), oleic acid are penetration enhancer for lamivudine into skin. Ethosomes were prepared with propylene glycol (ETP) and linoleic acid (ETL) respectively. Ethosomes bearing propylene glycol and oleic acid has shown good flux values 1.5 fold and 2 fold than ethosomes (ET) respectively. The highest entrapment efficiency of ETP-2 is 64.6&plusmn;1.5% and ETO-2 formulation is 68.2&plusmn;4.1%. Increases in the concentration of both permeation enhancers decrease the entrapment efficiency. The fluorescence skin <em>ex-vivo</em> study of the ethosomes formulation reveals that oleic acid ethosomes has deeper penetration in the skin compared to ethosomes containing propylene glycol. The release of the ETP-2 and ETO-2 has both shown sustain release pattern for 12 hrs with reduced in lag time. Ethosomes containing oleic acid has better entrapment, enhancement of lamivudine penetration to deeper skin compare ethosomes containing propylene glycol.&nbsp;</span></p>