Transdermal Drug Delivery System (TDDS) is an alternative to conventional delivery by lower the problems associated with the oral and parenteral administration of drugs. TDDS also bypasses the first pass metabolism effect that proved it suitability for low bioavailability drugs, to achieving a constant\controlled release of drug (especially for drugs having narrow therapeutic window) with minimize side effects attained by using variety of polymers (applied as a nano-carrier for microspheres, nanoparticles, gels etc. [1-5]). In TDDS route, drug molecules achieve a therapeutic amounts at their target site and skin application (limited due to the effective barrier properties of intact skin, primarily associated with the outermost layers of the epidermis, namely the stratum corneum) [6-10]. Also, there are numerous approaches have been adopted to overcome permeation problem associated with these routes, one such approach involves encapsulation of drug in a vesicular system i.e. a novel nano-carrier “nano-transfersomes” which is capable to improved transdermal delivery of drugs]  which are ultra-deformable lipid supra-molecular aggregates. They are capable to penetrating across the intact mammalian skin when applied nonocclusive by using a surface active agent added in a proper ratio [sublytic concentrations provided certain degree of flexibility to the vesicle membrane]. NTs claimed to be able to squeeze through channels one-tenth their diameter, allowing them to spontaneously penetrate the stratum corneum due to the flexibility. They penetrate across the skin by osmotic gradient (driving force), which is caused by the difference in water content between the relatively dehydrated skin surface (~20% water) and the aqueous viable epidermis. A lipid suspension when applied to the skin is subjected to evaporation [in order to avoid dehydration], NTs penetrates to the deeper tissues and hence squeeze through stratum corneum lipid lamellar regions penetrating deeper to follow the osmotic gradient [12,13].