Box-Behnken设计-效应面法优化吴茱萸碱-羟基乙酸共聚物纳米粒处方及体外释药研究

目的：Box-Behnken设计-效应面法优化吴茱萸碱聚乳酸-羟基乙酸共聚物poly （lactic-co-glycolic acid），PLGA]纳米粒处方（吴茱萸碱-PLGA纳米粒），考察体外释药行为。方法：单因素考察PLGA用量，油水体积比，泊洛沙姆188浓度，超声功率和时间等因素的影响，采用Box-Behnken响应面法优化吴茱萸碱-PLGA纳米粒处方。采用甘露醇为冻干保护剂，制备吴茱萸碱-PLGA纳米粒冻干粉末，并考察体外释药情况及释药模型。结果：吴茱萸碱-PLGA纳米粒最佳处方为：PLGA用量为445.1 mg、油水体积比1：5.2、泊洛沙姆188质量分数为1.2%。包封率和粒径分别为（75.73±1.33）%和（173.27±6.86） nm，与模型预测值接近。体外释药符合Higuchi模型：M_t/M_∞=0.109 9t^1/2+0.081 6，缓释特征明显。结论：Box-Behnken实验设计可用于吴茱萸碱-PLGA纳米粒处方研究，为进一步研究奠定了基础。

Formulation optimization of evodiamine-PLGA nanoparticles by Box-Behnken design-response surface method and in vitro release study

OBJECTIVE To employthe method of Box-Behnken design-response surface to optimize the formulation ofevodiaminepoly (lactic-co-glycolic acid), PLGA] nanoparticles (evodiamine-PLGA nanoparticles) and examine its in vitro release behavior.METHODS The effects of PLGA dosage, oil-to-water volume ratio, poloxamer 188 concentration, ultrasonic power and time were examined by single factor test.Box-Behnken design-response surface method was utilized for obtaining optimal formulation of evodiamine-PLGA nanoparticles. Mannitol was used as a freeze-dry protective agent for preparing freeze-dried powder of evodiamine-PLGA nanoparticles.The in vitro release behavior and release model were also explored.RESULTS The optimal formulation of evodiamine-PLGA nanoparticles:PLGA dosage was 445.1 mg, oil-water volume ratio 1:5.2 and poloxamer 188 concentration 1.2%. Envelopment efficiency and particle size were (75.73±1.33)% and (173.27±6.86) nm. Both were close to their predicted values. The drug release in vitro was conformed to the Higuchi model:M_t/M_∞=0.109 9t^1/2+0.081 6 and the process demonstrated obvious sustained-release characteristics.CONCLUSION It is feasible to apply Box-Behnken design-response surface method for formulation optimization of evodiamine-PLGA nanoparticles. It provides rationales for further researches.