Box-Behnken响应面法优化益母草碱脂质纳米粒处方

Formulation Optimization of Leonurine Lipid Nanoparticles by Box-Behnken Response Surface Methodology

关键词:  益母草碱  pH梯度结合逆向蒸发法  Box-Behnken效应面法  体外释放

Key words:  leonurine  pH-gradients method coupled with reverse evaporation method  Box-Behnken response surface method  in vitro release

摘要:

目的 制备益母草碱脂质纳米粒并优化处方。方法 采用pH梯度结合逆向蒸发法制备益母草碱脂质纳米粒，以粒径、包封率和载药量为评价指标，药物和脂质比例、胆固醇和脂质比例、药物终浓度为考察因素，采用Box-Behnken效应面法优化纳米粒处方，并考察纳米粒体外释放情况。结果 益母草碱脂质纳米粒最优处方为药物和脂质比例为9.8%，胆固醇和脂质为1.0%，药物终浓度为10 mg·mL^-1。制得的纳米粒粒径为（83.9±5.6）nm、包封率（73.3±2.2）%、载药量（4.0±0.0）%，实测值与预测值RSD均<5%。体外释放结果显示，与原料相比，益母草碱脂质纳米粒具有一定的缓释作用。结论 Box-Behnken响应面优化法应用简便、预测性好，所得益母草碱脂质纳米粒包封率和载药量高，符合设计要求。

Abstract:

OBJECTIVE To optimize the formulation of leonurine lipid nanoparticles.METHODS The leonurine lipid nanoparticles were prepared by pH-gradients method coupled with reverse evaporation method.Final drug concentration, drug-lipid ratio, cholesterol and lipid ratio were selected as influences factors, the formulation was optimized by Box-Behnken response surface method with particle, the particle size, encapsulation efficiency and loading content as the evaluation parameters.The in vitro release was determined.RESULTS The optimal formulation parameters were as follows: the drug-lipid ratio was 9.8%, cholesterol and lipid ratio was 1.0% and the final drug concentration was 10 mg·mL^-1.The mean particle size, entrapment efficiency, and the drug loading were (83.9±5.6)nm, (73.3±2.2)% and (4.0±0.0)%, respectively.RSD of measured and predicted values were all less than 5%.In vitro release test results showed that leonurine lipid nanoparticles had a sustained release effect compared with the raw materials.CONCLUSION The Box-Behnken response surface method is simple and predictable, and have high encapsulation efficiency and drug loading of the obtained leonurine lipid nanoparticles, which meets the design requirements.