目的 研究Pluronic L61修饰的聚丁二酸丁二醇酯(PBSu)载药纳米粒的制备及体外释放, 并评价纳米粒的细胞毒性, 为可生物降解PBSu材料在给药体系中的应用开辟途径。方法 通过乳化法制备L61-PBSu纳米粒, 以利福平为模型药物, 研究L61-PBSu纳米粒负载药物的体外释放, 并对药物释放进行动力学分析, 采用MTT染色法评价L61-PBSu纳米粒对人卵巢癌细胞(OVCAR-3)的细胞毒性。结果 纳米粒大小均匀, 载药后平均粒径在(140±7) nm。纳米粒能对药物进行有效包封, 包封率64.98%。累积释放率为90%时, 体外释放时间达到27 h, 药物释放机制遵循非Fick传输机制。纳米粒对OVCAR-3细胞毒性小, L61修饰后具有更低的细胞毒性。结论 L61-PBSu纳米粒制备简单, 生物相容性好, 对难溶性药物的缓释效果好, 是一种有前景的被动靶向载体新平台。
Abstract
OBJECTIVE To study the preparation of pluronic-modified biodegradable poly(butylene succinate) (PBSu) nanoparticles (NPs) and evaluate the release kinetics of the drug-loaded PBSu NPs and the cytotoxicity of the NPs, so as to provide a new platform for the application of biodegradable PBSu in drug delivery. METHODS Pluronic L61-modified PBSu NPs were prepared by emulsification method, and the morphology of the NPs was observed by transmission electron microscopy. The in vitro release kinetics of the rifampicin-loaded L61-PBSu NPs at 37 ℃ was studied. The cytotoxicity of the L61-PBSu NPs against human ovarian cancer cells (OVCAR-3) was evaluated by MTT assay. RESULTS The drug-loaded NPs had a unimodal distribution with an average size of (140±7) nm. The drug encapsulation efficiency attained 64.98%. The release time reached 27 h when the cumulative release percentage was 90%. The release kinetics followed non-Fickian mechanism. The NPs demonstrated very low cytotoxicity against OVCAR-3 cancer cells. Modification by L61 improved biocompatibility. CONCLUSION The Pluronic-modified PBSu NPs are easy to prepare, biocompatible, and show great promise as a new passive targeting platform for controlled release of insoluble drugs.
关键词
纳米粒 /
利福平 /
释放动力学 /
细胞毒性 /
可生物降解
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Key words
nanoparticle /
rifampicin /
release kinetics /
cytotoxicity /
biodegradability
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脚注
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基金
国家自然科学基金资助项目(21674063); 浙江省自然科学基金资助项目(LY12E03001)
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