星点设计-效应面法优化齐墩果酸乳铁蛋白纳米粒的处方

摘要

Objective: The aim of the study was to optimize the preparation parameters of oleanolic acid loaded lactoferrin - based nanoparticles (OA-Lf-NPs) by a central composite design- response surface method (CCD-RSM) for enhancing the dissolution of OA. Methods: In the formulation design using CCD-RSM, independent variables were concentration of Lf, pH of Lf solution and ratio of OA to Lf. Dependent variables were particle size, Zeta potential and entrapment efficiency of OA. Multilinear and quadratic poly-nomial regression were used to estimate the relationship between the dependent and the independent vari-ables. The optimized formulation was predicted by RSM and validated. Moreover, the transmission electron microgram was used to analyze the physicochemical characterization of OA-Lf-NPs. The in vitro dissolution was also investigated. Results: The results showed the fitting degree of quadratic polynomials were the highest in the dependent variables (R2>0.98). In the optimized formulation, the mean particle size was (203.4±8.3) nm, Zeta potential was (27.1±2.3) mV and the entrapment efficiency of OA was (92.6±3.2)%. The characterization results showed that the OA-Lf-NPs were spherical and exhibited a desirable increase of in vitro dissolution. Conclusion: It shows that the CCD-RSM established model was applicable in the optimization of OA-Lf-NPs. The above results will be the basis of the further study of improving the bioavailability of OA.%目的：采用星点设计-效应面法优化齐墩果酸乳铁蛋白纳米粒的处方，并对所制样品进行表征和体外溶出行为考察。方法：以乳铁蛋白浓度、pH值和药辅比为考察因素，粒径、Zeta电位、包封率为评价指标，采用多元线性回归及二次多项式回归建立指标与因素之间的数学关系，经效应面法预测最优处方并验证，对所得纳米粒制剂进行透射电镜及体外溶出度试验。结果：各项指标均以二次多项式方程拟合度最高（R2>0.98）且预测值与实测值吻合度较好，所制样品的平均粒径为（203.4±8.3） nm，Zeta电位为（27.1±2.3） mV，包封率为（92.6±3.2）%；表征结果显示纳米粒外观呈类球形；与原料药相比，纳米制剂溶出速率显著提高。结论：星点设计-效应面法适用于齐墩果酸乳铁蛋白纳米粒的处方优化筛选，并为进一步的体内生物利用度研究奠定了基础。