Percutaneous Delivery Application of Acylated Steric Acid-9-P(arginine) Cell Penetrating Peptides Used as Transdermal Penetration Enhancer++

Abstract

In this study, a cell-penetrating peptide named Acylated Steric acid-9 poly-arginine (r9-SA) was sucessfully synthesized. High performance liquid chromatography (HPLC) and mass spectrometry (MS) were used to characterize the structural formula of r9-SA. Diclofenac sodium was chosen as a model drug, and the transdermal permeation-enhancing effect of r9-SA was estimated in vitro. Skin irritation experiment and histopathological observation of tissue sections with HE and Masson staining were performed to analyze the security of r9-SA. The possible penetration-enhancing mechanism of r9-SA was characterized with laser scanning confocal microscopy (LSCM), differential scanning calorimetry (DSC), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and laser Raman spectroscopy, respectively. The in vitro penetration study showed that r9-SA has a promoting effect for enhancing the transdermal penetration of diclofenac sodium. Skin irritation experiment and histopathological observation results showed that r9-SA has good biocompatibility with skin. The experiments were carried on to characterize the penetration mechanism of r9 -SA. It was found that r9-SA may react with the keratin in the stratum corneum (SC), changing its secondary structure and so that drugs can penetrate through SC. In conclusion, all data showed that the r9-SA could be a safe and effective penetration enhancer for topical delivery of drug.