由于复杂的肠道环境、肠粘液层和上皮屏障的阻碍，口服紫杉醇（PTX）的生物利用度极低。因此，构建一种能够同时克服多个肠道物理化学障碍的协调递送系统具有重要意义。在本研究中，通过一种新型聚合物9-芴甲氧羰基聚乙二醇胆酸（Fmoc-PEG-GCA），制备了一种高密度PEG基糖胆酸装饰性胶束（PTX@GNPs）。该聚合物中的Fmoc基团可以通过π-π堆积包封PTX形成胶束的核心，Fmoc的低分子量和无长烃链保证了PEG的高密度。基于这种多功能、灵活的载体，PTX@GNPs具有灵活的PEG结构，能够逃逸黏液束缚，并且具有良好的肠道上皮靶向性，这得益于GCA与顶端钠依赖胆酸转运蛋白的高亲和力。体外与体内实验结果表明，这种口服胶束能够增强PTX的口服生物利用度，并通过静脉注射与Taxol具有类似的抗肿瘤疗效。此外，以更低剂量和更短间隔口服PTX@GNPs能够延长PTX在体内的持续时间，该效应有望通过协同作用改造免疫微环境并增强口服化疗疗效。©2023中国药学会和中国医学科学院药物研究所。由Elsevier B.V.制作和托管。

The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.