Department of Pharmaceutics, School of Pharmacy, China Medical University, Shenyang 110122, China.
Department of Sanitary Inspection, School of Public Health, Shenyang Medical College, No. 146 Yellow River North Street, Shenyang 110034, China.
Mol Pharm. 2020 Apr 6;17(4):1215-1225. doi: 10.1021/acs.molpharmaceut.9b01240. Epub 2020 Mar 19.
Inspired by the structure and function of the mussel adhesive protein, a facile strategy involving oxidative polymerization of dopamine was proposed for surface modification of nanostructured lipid carriers (NLCs) to promote drug delivery in the skin. The formation of a polydopamine (PDA) layer rounding the surface of NLCs was confirmed by the X-ray photoelectron spectroscopy and the Fourier transform infrared spectroscopy studies. Using terbinafine (TBF) as a model drug, the permeation study revealed that the PDA coating significantly enhanced the delivery of TBF from NLCs to the deep skin layers, where the follicular pathway played an essential role as suggested by the hair follicle blocking and differential tape stripping experiments, as well as the laser scanning confocal microscopy study by using Nile red as the fluorescent probe. The cellular investigation indicated that the PDA coating led to a higher cellular uptake of nanoparticles in human immortalized keratinocytes (HaCaT) without causing additional cytotoxicity. Using endocytic inhibitors, it was found that the lipid raft/caveolae-mediated endocytosis was strongly involved in the internalization of both the PDA modified and unmodified NLCs. Our results suggested that surface modification of NLCs with PDA coating improved the intracutaneous drug delivery mainly via the follicular pathway, which provided an avenue for the development of potential drug delivery carriers for dermal use.
受贻贝黏附蛋白的结构和功能启发，提出了一种简便的策略，即通过多巴胺的氧化聚合对纳米结构脂质载体（NLC）进行表面修饰，以促进药物在皮肤中的传递。通过 X 射线光电子能谱和傅里叶变换红外光谱研究证实了在 NLC 表面形成了聚多巴胺（PDA）层。使用特比萘芬（TBF）作为模型药物进行渗透研究表明，PDA 涂层显著增强了 TBF 从 NLC 向深层皮肤层的传递，毛囊途径在这一过程中发挥了重要作用，这一点可以通过毛囊阻塞和差异胶带剥离实验以及使用尼罗红作为荧光探针的激光扫描共聚焦显微镜研究得到证实。细胞研究表明，PDA 涂层导致人永生化角质形成细胞（HaCaT）中纳米颗粒的摄取率更高，而不会导致额外的细胞毒性。通过使用内吞抑制剂，发现 PDA 修饰和未修饰的 NLC 的内化均强烈涉及脂筏/小窝介导的内吞作用。我们的研究结果表明，用 PDA 涂层对 NLC 进行表面修饰主要通过毛囊途径改善了经皮药物传递，这为开发用于皮肤的潜在药物传递载体提供了新途径。
