Self-Assembled Palmitoyl-Glycine-Histidine as a Permeation Enhancer for Transdermal Delivery.

Abstract

The stratum corneum (SC) covers the outer surface of the skin and prevents the permeation of unwanted materials; however, the SC barrier also inhibits the desired permeation of active pharmaceutical ingredients (APIs). Therefore, the development of a novel method to enhance the permeation of APIs through the skin has been the focus of significant attention. Palmitoyl-glycine-histidine (Pal-GH)-comprising palmitic acid, glycine, and histidine-can be co-assembled with various additives to form a thixotropic hydrogel. Self-assembled Pal-GH enhances the permeation of ivermectin through the skin; however, the permeation mechanism is unclear and has not yet been discussed in detail. In the present study, the self-assembled structure of Pal-GH was analyzed using X-rays and infrared, and its permeation enhancement effect was verified. There was a correlation between the amount of Pal-GH in the skin and permeation enhancement, suggesting the involvement of the Pal-GH molecule. The presence of Pal-GH in the skin was confirmed by liquid chromatography-mass spectrometry and fluorescence labeling (labeling with Thioflavin T, a fluorescent dye that responds to β-sheets). The self-assembled Pal-GH permeated the SC without disrupting its organization. However, the structure of the Pal-GH caused changes to the lipid organization of the SC. The findings indicated that self-assembled Pal-GH is an effective permeation enhancer for transdermal delivery and does not induce skin irritation.