青蒿琥酯肠溶纤维的制备及体外释放研究

Study on Preparation and in Vitro Release of Artesunate-loaded Enteric Fibers

目的制备青蒿琥酯肠溶纤维,考察其体外释放行为。方法以尤特奇S100和L100-55为聚合物基质,添加一定量的青蒿琥酯,通过静电纺丝方法制备得到一系列载有青蒿琥酯的尤特奇纤维S100/ART和L100-55/ART。以紫外-可见分光光度法测定青蒿琥酯含量,计算S100/ART和L100-55/ART纤维的载药量和包封率,用扫描电子显微镜、热重分析仪对其形貌、热稳定性进行表征,用傅立叶变换红外光谱仪对药物在纤维载体中的状态进行表征,用溶出度测定仪以桨法测定其体外药物释放度。结果载药尤特奇纤维S100/ART和L100-55/ART结构均一,热稳定性良好,载药量可控,包封率高,药物以非晶态分散在纤维中;在pH 1.2人工胃液中释放的药物量较少,而在pH 6.8人工肠液中释放出大部分药物。在pH 1.2环境下S100/ART比L100-55/ART释放出更少的青蒿琥酯,在pH 6.8时释放出更多的青蒿琥酯。S100/ART和L100-55/ART亦具有一定的青蒿琥酯缓释作用。结论载药尤特奇纤维S100/ART和L100-55/ART可以用作青蒿琥酯肠溶制剂,作为青蒿琥酯肠溶纤维,S100/ART比L100-55/ART效果更好。制备得到的青蒿琥酯肠溶纤维,可以用于青蒿琥酯的肠道靶向递送和释放,有望提高青蒿琥酯的口服生物利用度。

OBJECTIVE To prepare artesunate-loaded enteric fibers and investigate their release behavior in vitro. METHODS A series of artesunate-loaded Eudragit fibers S100/ART and L100-55/ART were prepared by electrospinning, with Eudragit S100 and L100-55 as the polymer matrix and adding artesunate. The content of artesunate was determined by UV-Vis spectrophotometry, and the drug loading and entrapment efficiency of fibers S100/ART and L100-55/ART were calculated. The morphology and thermal stability of the fibers were characterized by SEM and TG, respectively. The physical status of artesunate in fibers was determined by FTIR. The in vitro drug release of the fibers was investigated by the paddle method using a dissolution tester. RESULTS The drug-loaded Eudragit fibers S100/ART and L100-55/ART had uniform structures, good thermal stability, controllable drug loading, and high entrapment efficiency. Artesunate was dispersed in fibers in amorphous state. Small amount of the drug were released from these fibers in the simulated gastric fluid of pH 1.2, while in the simulated intestinal fluid of pH 6.8 most of the drug were released. Moreover, S100/ART released less artesunate at pH 1.2 and more at pH 6.8 than L100-55/ART. S100/ART and L100-55/ART could also achieve the sustained release of artesunate. CONCLUSION The drug-loaded Eudragit fibers S100/ART and L100-55/ART can be used as enteric formulations of artesunate, and the artesunate-loaded enteric fiber S100/ART has better performance than L100-55/ART. The fabricated artesunate-loaded enteric fibers can be applied to achieve intestinal-targeted delivery and release of artesunate, and hopefully improve the oral bioavailability of artesunate.