Transdermal delivery of the tetrapeptide hisetal (melanotropin (6–9)). I. Effect of various penetration enhancers: in vitro study across hairless mouse skin

Abstract

The percutaneous absorption of the tetrapeptide hisetal as well as the effect of various penetration enhancers on the permeation of hisetal across hairless mouse skin was evaluated by in vitro methods in side-by-side diffusion cells (infinite dose technique). Although the molecular weight of the tetrapeptide is about 4-fold higher in comparison to the amino acids, the permeability coefficient of hisetal was found to be in the same order of magnitude as those of the amino acids. (5.58 × 10 −5 cm h −1). The permeation of hisetal was increased by enhancer treatment with oleic acid (3%) by a factor of 28. The relatively new permeation enhancer DDAA was found to increase the permeation of hisetal in concentrations of 3% to a higher extent (1.5-fold) than Azone ® at the same concentration. The mode of action of DDAA could not be determined by these investigations. However, it was shown that the DDAA effects as well as those of the other penetration enhancers were not reversible within 12 h. These findings lead to the assumption that DDAA induces its permeability enhancing effect on the basis of changes in the lipid structure of the stratum comeum similarly to Azone ® and oleic acid.