Department of Pharmacy, Guilin Medical University, Guilin, PR China.
Department of Pharmacy, Guangxi University of Chinese Medicine, Nanning, PR China.
Drug Deliv. 2020 Dec;27(1):575-584. doi: 10.1080/10717544.2020.1748762.
A delivery system based on l-carnitine (LC) conjugated chitosan (CS)-stearic acid polymeric micelles has been developed for improving the oral bioavailability of paclitaxel (PTX) through targeting intestinal organic cation/carnitine transporter 2 (OCTN2). Stearic acid grafted chitosan (CS-SA), as micelle skeleton material, was synthesized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. The PTX-loaded micelles were prepared by solvent evaporation-hydration method, and the ligand LC was conjugated onto the micelle surface by anchoring its derivative stearoyl group to the lipophilic core of micelle. The modified polymeric micelles showed regular spherical shapes with small particle size of 157.1 ± 5.2 nm and high drug loading capacity of 15.96 ± 0.20 wt%, and the micelle stability in water was supported by low critical micelle concentration of 14.31 ± 0.21 μg/ml. The drug-loaded micelles presented a slow and incomplete release, and the pharmacokinetic studies indicated the micelle carriers increased the relative bioavailability of PTX to 165.8% against the commercial formulation. The enhancement effect on intestinal absorption was also confirmed by the intracellular uptake of Caco-2 cells. The proposed micelle carrier system manifested a prospective tool for oral drug delivery.
基于左旋肉碱（LC）修饰壳聚糖（CS）-硬脂酸聚合物胶束的递药系统已被开发出来，通过靶向肠道有机阳离子/肉碱转运体 2（OCTN2）来提高紫杉醇（PTX）的口服生物利用度。硬脂酸接枝壳聚糖（CS-SA）作为胶束骨架材料，通过 1-乙基-3-（3-二甲基氨基丙基）碳二亚胺（EDC）介导的偶联反应合成。通过溶剂蒸发-水合法制备载药胶束，通过将 LC 的衍生物硬脂酰基锚定在胶束的疏水性核上，将 LC 连接到胶束表面。修饰后的聚合物胶束呈规则的球形，粒径为 157.1 ± 5.2nm，载药量为 15.96 ± 0.20wt%，载药胶束在水中的稳定性得益于低临界胶束浓度为 14.31 ± 0.21μg/ml。载药胶束呈现缓慢且不完全的释放，药代动力学研究表明，胶束载体使 PTX 的相对生物利用度提高到 165.8%，优于市售制剂。Caco-2 细胞的细胞内摄取也证实了该胶束载体对肠道吸收的增强作用。该胶束载体系统有望成为口服药物传递的工具。
