Hyaluronic Acid Micelles for Promoting the Skin Permeation and Deposition of Curcumin.

Abstract

BackgroundThe poor skin permeation and deposition of topical therapeutic drugs is a major issue in topical drug delivery, improving this issue is conducive to improving the topical therapeutic effect of drugs.MethodsIn this study, octadecylamine modified hyaluronic acid (OHA) copolymer was synthesized by amide reaction technique to prepare curcumin (CUR)-loaded micelles (CUR-M) for topical transdermal administration. CUR-M was successfully prepared by dialysis, and the formulation was evaluated for particle size, zeta potential, surface morphology, entrapment effciency (EE%), drug loading (DL), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and the in vitro drug release. Additionally, in vitro skin permeation and retention, in vivo topical analgesic and anti-inflammatory activity, and skin irritation were assessed.ResultsThe mean drug loading (DL), drug entrapment efficiency (EE), hydrodynamic diameter and zeta potential of CUR-M were 8.26%, 90.86%, 165.64 nm and −26.85 mV, respectively. CUR-M was characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), it was found that there was an interaction between CUR and OHA, and CUR existed in CUR-M in an amorphous form. CUR-M exhibited sustained release in 48 h and good stability at 4 °C for 21days. CUR-M could significantly increase the skin penetration and retention of CUR and had better analgesic and anti-inflammatory activities in vivo when compared with CUR solution. Hematoxylin-eosin staining results revealed that the transdermal penetration mechanism of CUR-M might be related to the hydration of stratum corneum by HA. In addition, CUR-M showed no skin irritation to mouse skin.ConclusionCUR-M might be a promising and safe drug delivery system for the treatment of topical diseases.