星点设计-效应面法优化阳离子纳米乳递送系统的处方工艺研究

Optimization of cationic nanoemulsion delivery system by star design-effect surface method

目的采用单因素试验和星点设计-效应面法优化阳离子纳米乳(CNE)的处方工艺,并对其药剂学性能进行评价。方法以平均粒径(D_(50))、粒径范围、离心稳定性常数(Ke)和电位为评价指标,单因素试验筛选CNE的油相种类、乳化剂种类及用量、甘油及十八胺用量、剪切时间,高压均质压力及时间,星点设计效应面法考察均质压力和时间对CNE的影响,用二项式及多元线性回归模型拟合建立指标与因素之间的关系,效应面法获取最佳处方。结果CNE最佳处方组成为中链脂肪酸甘油三酯(MCT)0.5 g,大豆卵磷脂1 g,十八胺53.90 mg,甘油0.8 g,其余为水相;最佳处方所得CNE外观基本圆整,澄清透明,D_(50)为(135.08±5.69)nm,Zeta电位为(43.57±2.51)mV,离心、稀释、时间稳定性均良好。结论优化得到的CNE为淡蓝色均一乳状液、稳定性良好粒径合适,可为核酸药物递送系统的开发提供参考。

Objective To optimize the formulation process of cationic nanoemulsion(CNE)and evaluate its pharmaceutical properties using single-factor test and star design-effect surface method.Methods With particle size(D_(50)),particle size range,centrifugal stability constant(Ke),and potential as the evaluation indexes,single-factor test was conducted to screen the type of oil phase,type and dosage of emulsifier,dosage of glycerol and Octadecanamine,shear time,high pressure,homogeneous pressure and time,and the effects of homogeneous pressure and time on CNE were investigated by Star point design effect surface method.Binomial and multiple linear regression models were used to establish the relationship between indexes and factors,and the optimal prescription was optimized by effect surface method.Results The optimum components of CNE included medium chain triglyceride(MCT)0.5 g,soy lecithin 1 g,octachylamine 53.90 mg,and glycerol 0.8 g;The rest was water phase.The appearance of the CNE was basically round,clear and transparent;D_(50) was(135.08±5.69)nm and Zeta potential was(43.57±2.51)mV,and the centrifugation,dilution,time stability were good.Conclusion The optimized CNE is a light blue homogeneous emulsion with suitable particle size and good stability,which can provide reference for the development of nucleic acid drug delivery system.