目的 采用Box-Behnken响应面法优化海藻酸钠聚乙二醇-聚乳酸-羟基乙酸共聚物(mPEG-b-PLGA)纳米粒的处方工艺。方法 合成10%mPEG5000-b-PLGA为基质材料,通过双乳剂法制备载胰岛素的海藻酸钠mPEG-b-PLGA纳米粒。选取胰岛素投料比、油相与外水相体积比、乳化剂浓度为考察因素,包封率和载药量为评价指标,采用Box-Behnken响应面法筛选最优处方,对优化所得纳米粒的基本性质和体外释药性能考察。结果 最优处方为:胰岛素投料比14.67∶100,油相与外水相体积比1∶3.32,乳化剂浓度为2.01%。实际制备所得载胰岛素纳米粒包封率为83.61%,载药量为10.90%,与模型预测值接近。平均粒径为(271.80±3.50)nm,Zeta电位值为-54.27 mV具有良好的缓释性能。结论 Box-Behnken响应面法有效可行,可以用于优化海藻酸钠mPEG-b-PLGA纳米粒的处方工艺,优化后的纳米粒有望作为理想的胰岛素缓释载体。
Abstract
OBJECTIVE To optimize the formulation of alginate mPEG-b-PLGA nanoparticles by Box-Behnken response surface method. METHODS Using synthetic 10% mPEG-b-PLGA as nanoparticles matrix materials, the insulin-loaded alginate mPEG-b-PLGA nanoparticles were prepared by modified double emulsion-solvent evaporation method.To optimize the formulation,the mass ratio of insulin to polymer,the volume ratio of oil phase to external water and the concentration of poloxamer 188(F68) were selected as independent variables, with encapsulation efficiency(EE%), loading capacity(LC%) as the dependent variables.The formula was optimized by Box-Behnken design and response surface methodology.The particles size, polydispersity index(PDI), Zeta potential and morphology of optimized nanoparticles were measured by dynamic light scattering(DLS), electrophoretic light scattering(ELS) and transmission electron microscope(TEM), respectively.The in vitro release profile of nanoparticles was investigated. RESULTS =The optimal formulation was as follows:the mass ratio of insulin to mPEG-b-PLGA was 14.67∶100, the oil phase to external water ratio was 1∶3.32 and F68(W/V) concentration was 2.01%, respectively. The entrapment efficiency, the loading capacity, average particles size and Zeta potentials were(83.61±0.38)%,(10.90±0.23)%,(271.8±3.5) nm and(-54.27±2.75) mV, respectively, which correspond closely to the predicted values.The optimized insulin-loaded nanoparticles performed good sustained release property in pH 7.4 medium. CONCLUSION The Box-Behnken design and response surface methodology is an effective and efficient method, which can be applied in the formula optimization of alginate mPEG-b-PLGA nanoparticles preparation.The optimized nanoparticles can be served as a promising insulin or proteins drug nanocarriers for its good sustained release property.
关键词
Box-Behnken /
响应面法 /
纳米粒 /
胰岛素 /
缓释 /
处方优化
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Key words
Box-Behnken /
response surface method /
nanoparticles /
insulin /
sustained release /
formula optimization
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中图分类号：
R944
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