Enhancing the skin permeation of testosterone with natural terpenes

Although a variety of chemical absorption enhancers (CAEs) have been included in transdermal preparations of testosterone (TST), local irritation or low efficacy of these agents have been often reported. In this context, three natural terpenes classified as safe by FDA were selected for this study, which could also provide secondary biological properties (e.g., antioxidant, anti-inflammatory and antimicrobial action). Ex vivo permeation studies were performed in the Franz-type diffusion cell model and human skin. An enhancement ratio of 7.61, 5.10 and 2.52 was achieved after treatment with carvacrol, α-bisabolol and menthol, respectively. Carvacrol provided higher permeation flux and cutaneous retention of TST than other terpenes. Mechanistic studies were also performed to evaluate the effect of CAEs on biophysical properties of the stratum corneum. Spectroscopic and thermal analyses showed structural changes in this tissue after all treatments and suggested that carvacrol causes a greater disorder in lipid domains. As this terpene affects the passive diffusion route more significantly (which is preferentially used by TST), it was considered the most effective CAE. Moreover, this agent could play a synergistic effect with TST in hypogonadism, but further studies are needed to prove the advantages of this association.