目的 制备左旋肉碱修饰的壳聚糖-硬脂酸（LC-SA/CS-SA）纳米胶束，包载紫杉醇（PTX）且协载槲皮素，考察胶束特性，并以大鼠在体肠循环评估给药系统对PTX口服吸收的促进作用。方法 将硬脂酸（SA）通过酰胺化反应接枝于壳聚糖（CS），形成共聚物CS-SA；采用核磁共振H谱、红外光谱鉴定产物结构；以PTX为主药，槲皮素为辅药，采用激光粒径分析、Zeta电位分析和HPLC分析分别考察了胶束的粒径、Zeta电位、载药量、包封率；透射电子显微镜观察胶束形貌；芘荧光探针法测定LC-SA/CS-SA胶束的临界胶束浓度（critical micelle concentration，CMC）；透析袋法考察胶束的体外释放行为；大鼠在体肠吸收实验评估载药胶束的促吸收作用。结果 红外与核磁结果表明SA通过酰胺键接枝于CS；协载槲皮素的LC-SA/CS-SA载PTX胶束呈类球形，粒径为（148.3±1.7）nm，多分散系数（PDI）为0.16±0.07，Zeta电位为（24.600±0.167）mV，CMC为14.31 μg/mL；体外释放结果表明，与市售紫杉醇注射剂相比，协载槲皮素的LC-SA/CS-SA载PTX胶束、LC-SA/CS-SA载PTX胶束具有明显缓释效应；大鼠在体肠吸收实验表明，协载槲皮素的LC-SA/CS-SA胶束对载药PTX的胃肠吸收具有显著促进作用。结论 构建的协载槲皮素的LC-SA/CS-SA载PTX胶束性能优良，促进了PTX的大鼠肠吸收，具有增强药物口服吸收潜力。

Objective To prepare a drug delivery system based on L-carnitine modified and quercetin (QUE)-coloading chitosan-stearic acid (LC-SA/CS-SA) nanomicelles, investigate the properties of micelles, and evaluate the enhanced absorption effect of the micelles by in vivo intestinal absorption in rats. Methods The CS-SA copolymer was synthesized by the amidation of free amino groups on CS. The chemical structure of CS-SA was characterized by Fourier transform-infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). Taking PTX was the main drug and quercetin as the auxiliary drug, the particle size distribution, Zeta potential, drug loading and entrapment efficiency of the micelles were investigated. The micromorphology of the micelles was observed by transmission electron microscope (TEM). The critical micelle concentration (CMC) of LC-SA/CS-SA micelles was measured by fluorescent probe method. The in vitro release of paclitaxel from polymeric micelles was evaluated by dialysis method. The absorption rate coefficient (K_a) of paclitaxel (PTX)-loaded micelles was assessed by in vivo intestine absorption in rats. Results The results of FT-IR and ¹HNMR indicated that the copolymer (CS-SA) was synthesized. The LC-SA/CS-SA@QUE+PTX micelles showed regular spherical shapes with particle size of (148.3±1.7) nm, PDI of 0.16±0.07, Zeta potential of (24.600±0.167) mV and CMC of 14.31 μg/mL. Compared to the commercial formulation of PTX, LC-SA/CS-SA@QUE+PTX micelles and LC-SA/CS-SA@PTX micelles showed significantly sustained release behaviors. The enhanced absorption effect of PTX in the micelle system was confirmed by intestine absorption test in rats. Conclusion The LC-SA/CS-SA@QUE+PTX micelles, as a potential oral absorption promoter, enhanced the intestinal absorption of PTX in rats.

R283.6

国家自然科学基金资助项目（81760718）；广西自然科学基金资助项目（2018GXNSFBA281044）；广西科技基地和人才专项（桂科AD19110070）；广西高等学校千名中青年骨干教师培育计划