Univ Lyon, Université Claude Bernard Lyon 1, CNRS, LAGEP UMR 5007, 43 Boulevard du 11 novembre 1918, F-69100 Villeurbanne, France; Canada Research Chair on Bio-inspired Materials and Interfaces, Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada; Laboratoire de Nanotechnologie Pharmaceutique, Faculté de Pharmacie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada.
Univ Lyon, Université Claude Bernard Lyon 1, CNRS, LAGEP UMR 5007, 43 Boulevard du 11 novembre 1918, F-69100 Villeurbanne, France.
Int J Pharm. 2018 Dec 20;553(1-2):120-131. doi: 10.1016/j.ijpharm.2018.09.046. Epub 2018 Oct 11.
We investigated the influence of nanoparticle (NP) surface composition on different aspects of skin delivery of a lipophilic drug: chemical stability, release and skin penetration. Cholecalciferol was chosen as a labile model drug. Poly(lactic acid) (PLA)-based NPs without surface coating, with a non-ionic poly(ethylene glycol) (PEG) coating, or with a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) coating were prepared using flash nanoprecipitation. Process was optimized to obtain similar hydrodynamic diameters. Polymeric NPs were compared to non-polymeric cholecalciferol formulations. Cholecalciferol stability in aqueous medium was improved by polymeric encapsulation with a valuable effect of a hydrophilic coating. However, the in vitro release of the drug was found independent of the presence of any polymer, as for the drug penetration in an intact skin model. Such tendency was not observed in impaired skin since, when stratum corneum was removed, we found that a neutral hydrophilic coating around NPs reduced drug penetration compared to pure drug NPs and bare PLA NPs. The nature of the hydrophilic block (PEG or PMPC) had however no impact. We hypothesized that NPs surface influenced drug penetration in impaired skin due to different electrostatic interactions between NPs and charged skin components of viable skin layers.
我们研究了纳米粒子（NP）表面组成对亲脂性药物皮肤传递的不同方面的影响：化学稳定性、释放和皮肤渗透。选择胆钙化醇作为不稳定的模型药物。使用闪蒸纳米沉淀法制备了无表面涂层的聚乳酸（PLA）基 NPs、具有非离子型聚（乙二醇）（PEG）涂层的 NPs 或具有两性离子聚（2-甲基丙烯酰氧基乙基磷酸胆碱）（PMPC）涂层的 NPs。对工艺进行了优化，以获得相似的水动力直径。将聚合物 NPs 与非聚合物胆钙化醇制剂进行了比较。通过聚合物包封可提高胆钙化醇在水介质中的稳定性，亲水性涂层具有重要作用。然而，体外药物释放与任何聚合物的存在无关，因为药物在完整皮肤模型中的渗透也是如此。在受损皮肤中没有观察到这种趋势，因为当去除角质层时，我们发现 NPs 周围的中性亲水性涂层会降低药物渗透，与纯药物 NPs 和裸 PLA NPs 相比。然而，亲水嵌段（PEG 或 PMPC）的性质没有影响。我们假设 NPs 表面由于活皮层的带电皮肤成分与 NPs 之间的不同静电相互作用而影响受损皮肤中的药物渗透。
