pH-时间双依赖型载药复合物的制备及其释药行为  

Preparation and Drug Release Behavior of pH-time Dual-dependent Drug Loaded Complex

作　　者：刘天宇 毕玉水 LIU Tianyu;BI Yushui(School of Chemistry and Pharmaceutical Engineering,Shandong First Medical University&Shandong Academy of Medical Sciences,Tai’an 271016,China)

机构地区：[1]山东第一医科大学(山东省医学科学院)化学与制药工程学院,山东泰安271016

出　　处：《中国现代应用药学》2023年第15期2124-2130,共7页Chinese Journal of Modern Applied Pharmacy

基　　金：山东省医药卫生科技发展计划面上项目(202013020767)。

摘　　要：目的 制备一种新型ZSM-5微孔分子筛基载药复合物,并考察其体外释药行为。方法 以ZSM-5微孔分子筛为载体,采用浸渍离心法将小分子抗肿瘤药物5-氟尿嘧啶(5-fluorouracil,5-FU)载入分子筛中,制备5-FU@ZSM-5初级药物组装体,再以提拉法于其表面利用天然有机高分子海藻酸钠(alginate,ALG)钙化覆膜,制备5-FU@ZSM-5@CaALG载药复合物。采用紫外分光光度法考察其载药率;利用X射线衍射、固体紫外-可见漫反射光谱、氮气等温吸脱附、扫描电镜、傅里叶变换红外光谱等手段对其结构和理化性质进行表征;通过体外释放度试验考察其释药性能。结果 紫外定量分析结果表明:载药复合物的载药率为11.7%。表征结果表明:小分子药物5-FU进入ZSM-5孔道,载药后未破坏ZSM-5的MFI拓扑结构。体外“时间-溶出介质变换”释放试验表明:与5-FU@ZSM-5组装体相比,5-FU@ZSM-5@CaALG载药复合物呈现出显著的pH-时间双依赖行为,其在人工胃液中2 h内累积释放率<10%,即>90%的药量能进入人工肠液,在人工胃肠液中48h内累积释放率为85.2%。结论 微孔ZSM-5分子筛可以作为5-FU优良的载体材料,配合CaALG可同时实现肠道定位给药和长效作用。OBJECTIVE To prepare a new ZSM-5 microporous molecular sieve based drug loaded composite and to investigate its drug release behavior in vitro.METHODS Using ZSM-5 microporous molecular sieve as carrier,a small molecule antitumor drug 5-fluorouracil(5-FU) was loaded into the molecular sieve by impregnation centrifugation and the primary drug assembly of 5-FU@ZSM-5 was prepared.Then,the surface of the primary drug assembly was coated with natural organic polymer sodium alginate(ALG) through calcification by lifting method,and the drug loaded complex of 5-FU@ZSM-5@CaALG was finally obtained.The drug loading rate of the drug loaded complex was investigated by UV spectrophotometry.The structure and physicochemical properties were characterized by X-ray diffraction,solid UV-VIS diffuse reflectance spectroscopy,nitrogen isothermal adsorption and desorption,scanning electron microscopy and Fourier transform infrared spectroscopy.The drug release performance of 5-FU@ZSM-5@CaALG was investigated by in vitro release degree experiment.RESULTS The results of UV quantitative analysis showed that the drug loading rate of the drug loaded complex was 11.7%.The characterization results showed that the small molecule drug 5-FU entered the ZSM-5 channel and did not destroy the MFI topology of ZSM-5 after drug loading.In vitro “time-dissolution medium transformation” release experiment showed that,compared with the drug assembly of 5-FU@ZSM-5,the drug loaded complex of 5-FU@ZSM-5@CaALG showed significant pH-time dual-dependent behavior.The cumulative release rate of the drug in the artificial gastric juice within 2 h was less than 10%,that is,more than 90% of the drug could enter the artificial intestinal juice.The cumulative release rate was 85.2% in artificial gastrointestinal fluid within 48 h.CONCLUSION Microporous ZSM-5 molecular sieve can be used as an excellent carrier material for 5-FU.In combination with CaALG,it can simultaneously achieve intestinal targeted drug delivery and long-term effect.

关 键 词：ZSM-5 微孔分子筛 浸渍离心法 肠道靶向递送系统 

分 类 号：R94[医药卫生—药剂学]