目的 制备以壳聚糖(chitosan,CS)修饰的降钙素/葛根素聚乳酸-羟基乙酸共聚物双载药纳米粒(chitosan-calcitonin/puerarin-PLGA-dual-loaded nanoparticles,CS-CT/PR-NPs),并考察其理化性质及体外释药特性。方法 以聚乳酸-羟基乙酸共聚物为载体材料,采用复乳溶剂蒸发法制备壳聚糖修饰的降钙素/葛根素聚乳酸-羟基乙酸共聚物双载药纳米粒;正交实验优化其处方工艺;透射电镜及激光粒度仪分别考察其形态、粒径和Zeta电位,高速离心法测定包封率及载药量双载药纳米粒;透析袋法考察其体外释药特性。结果 制备的壳聚糖修饰的降钙素/葛根素聚乳酸-羟基乙酸共聚物双载药纳米粒外观呈椭圆形,平均粒径为(190±2.65)nm,多分散指数为(0.117±0.027),Zeta电位为(16.5±1.08) mV,降钙素的包封率和载药量分别为(75.7±1.15)%,(3.47±0.31)%,葛根素的包封率和载药量分别为(50.9±1.08)%,(4.68±0.19)%;体外释药具有缓释特征。结论 本实验成功制备载有双药的壳聚糖修饰的降钙素/葛根素聚乳酸-羟基乙酸共聚物双载药纳米粒,2种药物的包封率均较高,体外释药均具有明显的缓释特征,为提高降钙素的口服生物利用度提供了可能,也为双载药纳米粒的制备提供实验参考。
Abstract
OBJECTIVE To prepare calcitonin/puerarin-PLGA-dual-loaded nanoparticles modified by chitosan, and investigate theirin vitro release behavior.METHODS CS-CT/PR-NPs were prepared by the double emulsion solvent evaporation technique with PLGA as a carrier material; the formulation of CS-CT/PR-NPs was optimized by orthogonal design; the morphology of CS-CT/PR-NPs was observed by transmission electron microscope;the mean particle size,particle size distribution and Zeta potential were measured by laser particle size analyzer; the entrapment efficiency and drug loading were measured by ultracentrifugation; the in vitro release behavior was studied by dialysis. RESULTS CS-CT/PR-NPs were spherical in shape with the mean particle size of(190±2.65) nm, particle size distribution of (0.117±0.027) and Zeta potentialof(16.5±1.08) mV. The entrapment efficiency was (75.7±1.15)%, and the drug loading of CT was (3.47±0.31)%, while those of PR were (50.9±1.08)% and (4.68±0.19)%, respectively. The profiles of in vitro release had the features of sustained-release. CONCLUSION CS-CT/PR-NPs are prepared successfully and show a sustained-release characteristic with high entrapment efficiency, which may improve the oral bioavailability of CT and provide the experimental reference for preparing the dual-loaded nanoparticles.
关键词
降钙素 /
葛根素 /
聚乳酸-羟基乙酸共聚物 /
双载药纳米粒 /
体外释药
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Key words
calcitonin /
puerarin /
PLGA /
dual-loaded nanoparticles /
in vitro release
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中图分类号：
R944
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参考文献
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脚注
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基金
浙江省自然科学基金资助项目(LQ15H280004)
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