载姜黄素形状记忆聚碳酸亚丙酯-聚乙二醇胃滞留给药系统的制备与评价  

Preparation and Evaluation of Curcumin-loaded PPC-PEG Shape Memory Gastroretentive Drug Delivery Systems

作　　者：郑威 宫苹 张紫微 周婉梅 陈宁[1] ZHENG Wei;GONG Ping;ZHANG Ziwei;ZHOU Wanmei;CHEN Ning(School of Pharmacy,Harbin University of Commerce,Harbin 150076,China)

机构地区：[1]哈尔滨商业大学药学院,哈尔滨150076

出　　处：《中国药学杂志》2025年第3期272-283,共12页Chinese Pharmaceutical Journal

基　　金：哈尔滨商业大学“青年科研创新人才”项目资助(2023-KYYWF-1037)。

摘　　要：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_PPCPEG),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48h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48h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(AUC_(0-24))和体内滞留时间(MRT_(0-24))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48h内具有良好的药物控释作用,药效时间长,生物利用度高。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(AUC_(0-24))and the retention time in vivo(MRT_(0-24))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 

分 类 号：R944[医药卫生—药剂学]