[关键词]
[摘要]
目的 制备壳聚糖修饰雷公藤多苷纳米粒(LMWC-TG-NPs),并研究其体外释药行为。方法 采用改良的自乳化溶剂扩散法制备LMWC-TG-NPs;正交试验设计优化雷公藤多苷纳米粒(TG-NPs)处方,单因素试验考察壳聚糖(LMWC)修饰方式;以含20%乙醇的PBS(pH 7.4)为释放介质考察LMWC-TG-NPs的体外释药行为。结果 优化的处方工艺:以1.0% Poloxamer 188、80 mg PLA、12 mL有机相、丙酮-乙醇(2∶3)制备TG-NPs混悬液,以与TG-NPs混悬液等体积的10% LMWC溶液修饰TG-NPs制备LMWC-TG-NPs;根据优化条件制备的LMWC-TG-NPs,外观呈圆形或类圆形,平均粒径为(207.6±3.4)nm,多分散指数(PDI)为0.078±0.009(n=3),包封率和载药量分别为(61.83±2.43)%、(10.70±0.37)%(n=3);体外释药符合Higuchi方程。结论 所制备的LMWC-TG-NPs包封率较高,粒径小,体外释药具有明显的缓释特征,为后期研究其肾脏靶向和毒性奠定了基础。
[Key word]
[Abstract]
Objective To prepare tripterygium glycosides-loaded nanoparticles modified by 50% N-acetylated low molecular weight chitosan (LMWC-TG-NPs) and to investigate their in vitro release behavior. Methods The LMWC-TG-NPs were prepared by modified self-emulsifying solvent diffusion method; The formulation of TG-NPs was optimized by orthogonal design and the modified condition of LMWC was determined based on the single factor analysis. The in vitro drug release of LMWC-TG-NPs was characterized with PBS (pH 7.4) containing 20% ethanol. Results The optimized formulation of TG-NPs was as follows: Poloxamer 188 (1.0%), PLA (80 mg), organic phase (12 mL), and acetone-ethanol (2∶3) were used to prepare TG-NPs suspension. The LMWC-TG-NPs were prepared by incubating TG-NPs suspension with 10% LMWC solution at the ratio of 1∶1. The shape of the prepared LMWC-TG-NPs was spherical. The mean particle size, polydispersity index, entrapment efficiency, and drug loading were (207.6 ± 3.4) nm, 0.078 ± 0.009, (61.83 ± 2.43)%, and (10.70 ± 0.37)% (n=3), respectively. The in vitro release characteristics of LMWC-TG-NPs conform to Higuchi equation in PBS buffer composed of 20% ethanol at pH 7.4. Conclusion The prepared LMWC-TG-NPs show a sustained-release characteristics with well-distributed particle size as well as high entrapment efficiency and drug loading, which could lay the foundation for the research on kidney targeting and toxicity.
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[基金项目]
国家自然科学基金资助项目(30902007);浙江省重点科技创新团队资助项目(2012R10044-05)