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The need for smaller, more elastic carriers led to the development of the second generation of vesicular-based lipid carriers, transferosomes, also termed ultra-deformable liposomes [37]. In 1992, Cevc and Blume [38] introduced the transfersomes, which resemble liposomes in morphology but are more lipophilic, smaller than 300 nm, and are at least one order of magnitude more elastic than liposomes. Furthermore, when compared to liposomes, transfersomes contain one or more edge-activator substance(s), surfactants being the most commonly used edge-activators. Edge-activators typically used for ultra-deformable liposome preparation include sodium cholate, sodium deoxycholate, Span 60, Span 65, Span 80, Tween 20, Tween 60, Tween 80, and dipotassium glycyrrhizinate [37]. There are 2 major proposed mechanisms of skin delivery via ultra-deformable liposomes [37, 39]. The first mechanism proposes that the deformable nature of the intact vesicles contributes to their entry into the SC. The second mechanism proposes that vesicles act as penetration enhancers, whereby vesicles modify the intercellular lipids of the SC. Because their transport across the skin is driven by a hydration gradient, occlusive application can compromise the action of the deformable vesicles by eliminating the gradient force. One disadvantage of these vesicles corresponds to the difficulty in loading hydrophobic drugs into the vesicles without compromising their deformability and elastic properties [39].