Objectives: To formulate and investigate the role of various penetration enhancers in the transfersomal gel delivery of adapalene. Methods: Transfersomes were formulated by reverse-phase evaporation method and the influence of various parameters was investigated and optimized for particle size, PDI, zeta potential, and entrapment efficiency using the Design of Experiment approach. Optimized formulation was subjected to various characterizations such as Fourier Transform Infrared Spectroscopy, turbidity measurement, and deformability study, and then transfersomes were incorporated into a suitable gel (Carbopol 934). The transfersomal gel was then characterized for gel characteristics such as pH, spreadability, viscosity, homogeneity, extrudability, etc. Appropriate essential oils used as natural permeation enhancers like eucalyptus oil, menthol, peppermint oil, and turpentine oil were included in the transfersomal gel of adapalene, and then in vitro drug release, ex vivo permeation, and flux study was conducted and compared. Results: The adapalene loaded transfersomal gel showed particle size of 152.1 nm, PDI of 0.315, the zeta potential of -42.9 mV, and entrapment efficiency of 58.65 %. FTIR studies showed no interactions among the drug, lipids, and polymers used. Among the essential oils used as the permeation enhancers, the formulations containing peppermint oil displayed better in vitro drug release and ex vivo permeation than the other formulations containing remaining essential oils. Conclusion: From the present study, it can be concluded that the developed formulation can enhance the topical penetration of the drug and thereby improve therapy, which certainly adds quality to the transfersomal preparation.
Key words: Transfersomes, Adapalene, Eucalyptus oil, Turpentine oil, Menthol oil, Peppermint oil.