A transferosome is the first generation of an elastic liposome prepared from phospholipids and edge activators. An edge activator is often a single-chain surfactant with a high radius of curvature that destabilizes the lipid bilayers of vesicles and increases the deformability of the bilayers, thereby making the vehicle ultra-deformable. Acyclovir is a synthetic purine nucleoside analog derived from guanine, is the most widely used antiviral agent. It is effective in the treatment of herpes simplex virus (HSV), mainly HSV-1 and HSV-2 and varicella-zoster virus. However, it has low skin permeability. Hence, the objective of this study was to prepare acyclovir using transferosomes to overcome the barrier function of the skin. The present study deals with the development of transferosomal gel containing acyclovir by handshaking method for painless acyclovir delivery for use in the treatment of skin disease through 33 Fractional factorial design in which amount of Phospholipid (A), Cholesterol (B) and Tween 80 (C) was selected as independent variables and vesicle size (X1) Polydispersity index (X2) and %entrapment efficiency (X3) as dependent variables. The prepared transferosomes were evaluated with respect to entrapment efficiency (EE %), particle size, and quantity of in vitro drug released to obtain an optimized formulation. The optimized formulation of acyclovir transferosomes was incorporated into a Carbapol 934 gel base which was evaluated for drug content, pH, spreadability, viscosity and in vitro permeation. The prepared acyclovir transferosomes had a high EE% ranging from 65 to 81%, with small particle sizes ranging from 181.9 to 401.8nm. The in vitro release study suggested that there was an inverse relationship between EE% and in vitro release. The formulation TF2 have better in-vitro drug release profile which contains carbopol 980 concentration 2 %w/w. The kinetic analysis of release profiles of TF2 was found to follow the Korsmeyer-Peppas model. All independent variables had a significant effect on the dependent variables (p-values < 0.05). Therefore, acyclovir in the form of transferosomes can penetrate the skin, overcoming the stratum corneum barrier.
 
