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

Jiangxiu Niu,* Ming Yuan,* Zhaowei Zhang, Liye Wang, Yanli Fan, Xianghui Liu, Xianming Liu, Huiyuan Ya, Yansong Zhang, Yang Xu College of Food and Drug, Henan Functional Cosmetics Engineering & Technology Research Center, Luoyang Normal University, Luoyang, 471934, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liye Wang; Xianming Liu, Email liye2009314@163.com; myclxm@163.comBackground: The 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.Methods: In 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.Results: The 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 revea