载大黄素形状记忆胃滞留复合膜的制备及其功效评价  

Preparation of composite membrane in emodin-containing shape memory gastric retention and efficacy evaluation

作　　者：张卓[1] 王怡[1] ZHANG Zhuo;WANG Yi(Harbin University of Commerce,Harbin 150028)

机构地区：[1]哈尔滨商业大学,哈尔滨150028

出　　处：《中南药学》2024年第10期2609-2617,共9页Central South Pharmacy

基　　金：国家级大学生创新创业训练计划项目(No.202210240059);黑龙江省自然科学基金优秀青年项目(No.YQ2022H002)。

摘　　要：目的制备载大黄素形状记忆胃滞留复合膜,对其体外抑制SGC-7901胃癌细胞增殖效果进行评价,并对其复合膜胃滞留效果和生物利用度进行评价。方法以复合膜的漂浮时间、形变恢复、复合膜中大黄素的体外累计释放率为指标,考察膜剂主要材料聚乳酸(PLA)与聚碳酸亚丙酯(PPC)的最佳配比。采用CCK-8法和细胞划痕实验评价载药复合膜抑制胃癌细胞增殖的效果。利用HPLC技术对最佳载药复合膜PLA/PPC(6/4)@SD在大鼠体内的药动学进行研究。利用活体成像技术检测药物在小鼠体内的滞留情况,对固体分散体(SD)和PLA/PPC(6/4)@SD在小鼠体内的胃滞留情况进行分析。结果通过工艺优化发现PLA与PPC的最佳配比为6∶4,复合膜持续漂浮时间>12 h,其在人体适应温度(37℃)时复合膜的形变恢复可达79%,24 h体外药物释放率达57.36%。体外实验结果表明载大黄素复合膜对SGC-7901胃癌细胞具有明显的抑制作用。药动学实验结果表明PLA/PPC(6/4)@SD可有效改善大黄素在大鼠体内的生物利用度,与大黄素(EMO)相比,生物利用度提高375%,与SD组相比,生物利用度提高166%。PLA/PPC(6/4)@SD组胃滞留时间可达12 h。结论本研究制备的载大黄素形状记忆胃滞留复合膜可以延长大黄素在胃部的滞留时间,提高大黄素的生物利用度,可有效抑制SGC-7901胃癌细胞增殖,从而对胃癌的辅助治疗具有一定的意义。Objective To determine the inhibitory effect of emodin-containing shape memory gastric retention composite membrane on the proliferation of SGC-7901 gastric cancer cells in vitro,and evaluate the efficacy of gastric retention and bioavailability of composite membrane.Methods The optimal ratio of polylactic acid(PLA)to poly-propylide carboxate(PPC)was based on floating time,shape recovery and cumulative release rate of emodin in the composite membrane.CCK-8 method and cell scratch test were used to evaluate the inhibitory effect of composite membrane on the proliferation of gastric cancer cells.The pharmacokinetics of the best composite membrane PLA/PPC(6/4)@SD in rats were studied by HPLC.The gastric retention of solid dispersion(SD)and PLA/PPC(6/4)@SD in mice was analyzed by in vivo imaging.Results The optimal ratio of PLA to PPC in the composite membrane was 6∶4,its continuous floating time was longer than 12 h,the deformation recovery of the composite membrane reached 79%at 37℃,and the drug release rate was up to 57.36%after 24 h.The in vitro experiments showed that emodin-containing composite membrane had obvious inhibition on SGC-7901 gastric cancer cells.The pharmacokinetic experiment showed PLA/PPC(6/4)@SD effectively improved the bioavailability of emodin in rats,and the bioavailability increased by 375%as compared with emodin(EMO)and 166%as compared with SD group.The gastric retention time of PLA/PPC(6/4)@SD group could reach 12 h.Conclusion The prepared emodin-containing shape memory gastric retention membrane can prolong the retention time of emodin in the stomach,improve the bioavailability of emodin,and effectively inhibit SGC-7901 gastric cancer cells,serving as an adjuvant treatment of gastric cancer.

关 键 词：形状记忆聚合物 大黄素 胃癌 活体成像 

分 类 号：R283[医药卫生—中药学] R285[医药卫生—中医学]