四环素介导的骨靶向嫁接物胶束的制备及体外评价

发布时间：2019-07-21 21:09

【摘要】：目的制备四环素介导的聚乙二醇-聚(乳酸-羟基乙酸)载阿托伐他汀(TC-PEG-PLGA/ATO)胶束,并且考察载药胶束的理化性质及其体外靶向性。方法通过脱水反应合成具有两亲性的TC-PEG-PLGA嫁接物并对其进行结构确证,利用透析法实现对水难溶性药物阿托伐他汀的负载,采用透射电镜观察载药胶束的形态,激光粒度分析仪测定载药胶束的粒径和Zeta电位,HPLC测定胶束载药量和包封率,透析法考察载药胶束的体外释放行为。对TC-PEG-PLGA嫁接物胶束的体外细胞毒性(MTT法)和羟基磷灰石靶向能力进行评价。结果本实验成功制备了TC-PEG-PLGA/ATO载药胶束,其平均粒径为(47.2±4.7)nm,电位值为(-14.25±0.31)mV,包封率为(98.2±1.51)%,载药量为(8.71±0.23)%,体外释放研究表明,48 h时药物的累计释放率接近70%,具有明显的缓释作用。MTT结果表明,空白胶束在100~500μg·mL~(-1)内生物相容性良好。骨靶向TC-PEG-PLGA胶束(87.94%)的羟基磷灰石亲和能力相比于比PEG-PLGA胶束(18.59%)提高了4.73倍。结论本实验成功构建TC-PEG-PLGA/ATO载药胶束,其粒径小,稳定性好,可显著提高ATO在水相中的浓度,在体外具有良好的缓释效果、安全性及对羟基磷灰石的亲和力。
[Abstract]:Objective to prepare polyethylene glycol-polylactic acid (lactic acid-glycolic acid) loaded atovastatin (TC-PEG-PLGA/ATO) micelle mediated by tetracycline, and to investigate the physical and chemical properties and in vitro targeting of drug-loaded micelle. Methods Amphiphilic TC-PEG-PLGA grafting was synthesized by dehydration reaction and its structure was confirmed. The morphology of drug-loaded micelle was observed by transmission electron microscope, the particle size and Zeta potential of drug-loaded micelle were measured by laser particle size analyzer, the drug loading and entrapment efficiency of micelle were measured by HPLC, and the release behavior of drug-loaded micelle in vitro was investigated by dialysis. The cytotoxicity (MTT assay) and hydroxyapatite targeting ability of TC-PEG-PLGA grafting micelle in vitro were evaluated. Results the average particle size of TC-PEG-PLGA/ATO micelle was (47.2 卤4.7) nm, and the entrapment efficiency was (98.2 卤1.51)%, and the drug loading was (8.71 卤0.23)%. The results of in vitro release showed that the cumulative release rate of the drug was close to 70% at 48 h, and the drug release rate was obviously sustained-release. The results showed that the entrapment efficiency was (98.2 卤1.51)% and the drug loading rate was (8.71 卤0.23)% at 48 h, and the drug release rate was close to 70% at 48 h, which showed that the drug release rate was close to 70% at 48 h. The blank micelle has good biocompatibility in 100 ~ 500 渭 g 路mL ~ (- 1). The affinity of hydroxyapatite targeting TC-PEG-PLGA micelle (87.94%) was 4.73 times higher than that of PEG-PLGA micelle (18.59%). Conclusion the micelle loaded with TC-PEG-PLGA/ATO has been successfully constructed with small particle size and good stability. It can significantly increase the concentration of ATO in aqueous phase and has good sustained release effect, safety and affinity to hydroxyapatite in vitro.
【作者单位】：华中科技大学同济医学院附属武汉中心医院药剂科;阳江市人民医院;
【分类号】：R943

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