目的 姜黄素(Cur)具有良好的抗胃癌活性,但因其水溶性差,碱性pH条件下易降解,限制其在临床上的应用。本课题通过制备载Cur形状记忆聚碳酸亚丙酯-聚乙二醇(PPC-PEG)新型胃滞留给药系统来提高Cur的体内生物利用度。方法 制备Cur环糊精包合物(Cur_β-CD)并负载到PPC-PEG复合薄膜上,制备出可形变展开型胃滞留给药系统(Cur_β-CD_PPC-PEG),并对其进行特性表征、体外人胃癌细胞(SGC-7901)增殖抑制分析和大鼠体内药动学分析等。结果 经环糊精包合后,Cur_β-CD水溶性是Cur原料药的35.85倍。复合薄膜PPC-PEG(7.5∶2.5)在37 ℃条件下的形变恢复率为88.6%;将Cur_β-CD负载于PPC-PEG后,Cur与复合薄膜为物理共混,负载后的Cur热稳定性良好;Cur的载入对PPC-PEG载体的形状记忆性能产生一定的影响,但仍满足作为形变胃滞留剂型对形变恢复率的要求。Cur_β-CD_PPC-PEG胃滞留给药系统体外释药48 h的累积释放率为71.42%。Cur_β-CD_PPC-PEG体外抑制胃癌SGC-7901细胞增殖效果良好,作用48 h的细胞增殖抑制率可达86.64%。药动学结果表明,Cur_β-CD_PPC-PEG药-时曲线下面积 ( AUC0-24)和体内滞留时间(MRT0-24)分别是Cur的9.73倍和2.95倍。结论 本研究成功制备出一种新型的基于形状记忆PPC-PEG复合膜的载Cur_β-CD胃滞留递药系统,该系统在48 h内具有良好的药物控释作用,药效时间长,生物利用度高。
Abstract
OBJECTIVE To develop a novel gastric retention drug delivery system incorporating curcumin(Cur), based on the shape memory polypropylene carbonate-polyethylene glycol (PPC-PEG), with the objective of enhancing the in vivo bioavailability of Cur. METHODS The curcumin-cyclodextrin inclusion complex (Cur_β-CD) was prepared and loaded onto the shape memory polypropylene carbonate-polyethylene glycol composite film (PPC-PEG) to create the expanded gastric retention drug delivery system (Cur_β-CD_PPC-PEG); multiple characterization, proliferation inhibition analysis of human gastric cancer cells (SGC-7901) in vitro, and pharmacokinetics analysis in rats were then performed. RESULTS After cyclodextrin inclusion, the water solubility of Cur_β-CD was 35.85 times higher than that of Cur. The deformation recovery rate of the composite film PPC-PEG(7.5∶2.5) is 88.6% at 37 ℃. The Cur was physically incorporated into the composite film of Cur_β-CD_PPC-PEG, and the loaded Cur exhibited excellent thermal stability. The loaded Cur has a certain effect on the shape memory performance of PPC-PEG; however, it still satisfies the requirement for deformation recovery rate as a deformable gastric retention formulation. The in vitro cumulative release rate of Cur_β-CD_PPC-PEG over a 48-hour period was determined to be 71.42%. The Cur_β-CD_PPC-PEG exhibits significant efficacy in vitro against the proliferation of gastric cancer SGC-7901 cells, with a remarkable inhibitory rate of 86.64% observed after 48 h of treatment. The pharmacokinetic results showed that the area under the curve (AUC0-24) and the retention time in vivo (MRT0-24) of Cur_β-CD_PPC-PEG were 9.73 times and 2.95 times higher than those of Cur. CONCLUSION In this study, a novel shape memory gastric retention drug delivery system of Cur_β-CD_PPC-PEG is successfully prepared. The system exhibits a favorable drug controlled release effect within 48 h, characterized by rapid onset, prolonged duration of efficacy, and high bioavailability.
关键词
姜黄素 /
包合物 /
形状记忆复合物 /
胃滞留给药系统 /
SGC-7901细胞
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Key words
curcumin /
inclusion complex /
shape memory complex /
gastric retention drug delivery system /
SGC-7901 cell
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参考文献
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脚注
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基金
哈尔滨商业大学“青年科研创新人才”项目资助(2023-KYYWF-1037)
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