Wang Xin, Chen Yangnan, Liu Yan, Wu Danqing, Long Yanqiu, Gui Shuangying, Zheng Zhiyun, He Ning
Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, China.
Institute of Pharmaceutics, Anhui Academy of Chinese Medical Sciences, Hefei, China.
Biopharm Drug Dispos. 2025 Feb;46(1):10-21. doi: 10.1002/bdd.70000. Epub 2025 Mar 4.
The aim of this study was to improve the penetration of betulinic acid (BA) into skin efficiently by incorporating it into a nanostructured lipid carrier (NLC)-based gel. BA-NLC was prepared by the melt-emulsification and low-temperature solidification method. The optimized formulation was incorporated into the hydrogel and evaluated for pH, in vitro release, occlusion factor, and dermatokinetics. Furthermore, the transdermal penetration mechanism of the NLC gel was investigated by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), skin histological staining, and fluorescence microscopic methods. The optimized NLC showed a particle size of 153.40 nm and a high EE of 86.21%. In vitro drug release behavior of the BA-NLC gel showed higher cumulative release at 24 h (67.17 ± 2.39%) compared to the free drug (57.53 ± 2.17%). In vivo dermatokinetic studies disclosed that the BA-NLC gel presented elevated C and AUC in the epidermis and dermis in contrast to the conventional gel. FT-IR and DSC research indicated that the NLC formulations changed the configuration of skin keratin and augmented lipid fluidity, thus facilitating the percutaneous permeability of actives. Fluorescence microscopy also indicated improved skin penetration of the BA-NLC gel. Hence, the optimized NLC gel could potentially be a promising drug nanocarrier to boost skin drug penetration and retention.
本研究的目的是通过将桦木酸（BA）载入基于纳米结构脂质载体（NLC）的凝胶中，有效提高其皮肤渗透性。采用熔融乳化和低温固化法制备BA-NLC。将优化后的制剂载入水凝胶中，并对其pH值、体外释放、封闭因子和皮肤动力学进行评估。此外，通过傅里叶变换红外光谱（FT-IR）、差示扫描量热法（DSC）、皮肤组织学染色和荧光显微镜方法研究了NLC凝胶的透皮渗透机制。优化后的NLC粒径为153.40 nm，包封率高达86.21%。与游离药物（57.53±2.17%）相比，BA-NLC凝胶的体外药物释放行为在24 h时累积释放率更高（67.17±2.39%）。体内皮肤动力学研究表明，与传统凝胶相比，BA-NLC凝胶在表皮和真皮中的C和AUC升高。FT-IR和DSC研究表明，NLC制剂改变了皮肤角蛋白的构象，增加了脂质流动性，从而促进了活性成分的经皮渗透性。荧光显微镜也表明BA-NLC凝胶的皮肤渗透性得到改善。因此，优化后的NLC凝胶可能是一种有前途的药物纳米载体，可提高皮肤药物的渗透性和滞留性。
