星点设计效应面法优化葛根素改性壳聚糖纳米粒的处方与工艺研究

Preparation of Puerarin Modified Chitosan Nanoparticles by Central Composite Design of Response Surface

目的:筛选葛根素改性壳聚糖纳米粒的最优处方与工艺。方法:采用星点设计效应面法优化葛根素改性壳聚糖纳米粒制备工艺,以改性壳聚糖(SA-CS)质量浓度、壳聚糖pH值、TPP质量浓度、PEG 2000加入量、温度、搅拌速度、搅拌时间为考察因素,以粒径、多分散指数(PDI)、电位、包封率、载药量为评价指标,进行单因素考察。采用星点设计效应面法筛选最优处方。选取常用冻干保护剂甘露醇、蔗糖、乳糖和葡萄糖对葛根素改性壳聚糖纳米粒的冻干保护进行考察。结果:优化后离子凝胶化法最优的处方为SA-CS浓度为2.5 mg/mL,SA-CS的pH为6.05,TPP浓度为0.50 mg/mL,PEG的浓度为5%,为了方便实验操作,将最优处方和工艺定为SA-CS浓度为2.5 mg/mL,SA-CS的p H为6.00,TPP浓度为0.50 mg/mL,PEG的浓度为5%。冻干保护结果显示质量分数为5%甘露醇对SA-CS-Pur-NPs的保护最佳。结论:采用星点设计效应面法优化得到葛根素改性壳聚糖纳米粒的处方,通过甘露醇进行冻干得到的纳米粒外观饱满,复溶性好,稳定性得到显著提高。

Objective:To optimize the preparation of puerarin-modified chitosan nanoparticles.Methods:The SA-CS-Pur-NPS was prepared by the ion cross-linking method.The main factors including the concentration of SA-CS,the concentration of TPP,the pH of SA-CS,the stirring time,the stirring temperature,the stirring speed,and the amount of PEG 2000 were investigated.The evaluation is based on particle size,PDI,potential,encapsulation efficiency,and drug loading.Central composite design response surface method was employed to optimize formulation,Central Composite Design response surface design method was employed as evaluation index to investigate the optimal prescriptions.The freeze-drying protection of Puerarin modified chitosan nanoparticles was investigated by selecting common freeze-drying protectants mannitol,sucrose,lactose and glucose.Results:The optimal formulation was as following:SA-CS was 2.5 mg/mL,the pH of SA-CS was 6.05,the concentration of TPP was 0.50 mg/mL,and the concentration of PEG was 5%.In order to facilitate the experiment Operation,the optimal prescription and process was set as SA-CS concentration of 2.5 mg/mL,SA-CS pH of 6.00,TPP concentration of 0.50 mg/mL,and PEG concentration of 5%.The freeze-drying investigation of SA-CS-Pur-NPS showed that the mass concentration 5%of mannitol can well protect the shape and properties of SA-CS-Pur-NPS.Conclusion:The formulation of Puerarin modified chitosan nanoparticles is optimized by central composite design and response surface methodology.The nanoparticles obtained by freeze-drying with mannitol has full appearance,good resolubility and better stability.