酒石酸长春瑞滨壳聚糖纳米粒的制备及质量评价

Preparation and quality evaluation of vinorelbine bitartrate-loaded chitosan nanoparticles

目的制备酒石酸长春瑞滨壳聚糖纳米粒(Vin-loaded CNs)并评价其质量。方法采用离子胶凝化法制备Vin-loaded CNs,以壳聚糖质量浓度(X_1)、三聚磷酸钠的质量浓度(X_2)和搅拌时间(X_3)作为考察因素,以平均粒径(Y_1)和包封率(Y_2)作为评价指标,使用Box-Behnken实验设计进行处方优化,采用激光粒度仪测定粒径分布、多聚分散系数(PdI)和ζ电位,透射电镜观察其微观形态;比较Vin-loaded CNs在pH值为7.4的磷酸盐(PBS)缓冲液和大鼠血浆中的释药速率。结果优化得到Vin-loaded CNs的最优处方为:壳聚糖质量浓度为0.50 mg·mL^(-1),三聚磷酸钠质量浓度为0.49 mg·mL^(-1),搅拌时间为60 min,Vin-loaded CNs的包封率为77.8%±1.6%;平均粒径为391.6±6.3 nm,ζ电位为23.2±2.6 mV;用透射电镜可观察到Vin-loaded CNs呈近似球形分布,粒径较均匀;在pH值为7.4 PBS缓冲液和大鼠血浆中释药平缓。结论将酒石酸长春瑞滨制成壳聚糖纳米粒稳定性好,体外释药缓慢,有望提高药物疗效。

Objective To prepare vinorelbine bitartrate-loaded chitosan nanoparticles (Vin-loaded CNs) and evaluate its physical and chemical properties.Methods The Vin-loaded CNs were prepared by iron gelation method.The chitosan mass concentration ( X 1 ),sodium tripolyphosphate concentration ( X 2 ) and stirring time ( X 3 ) were used as independent variables.The average particle size ( Y 1 ) and encapsulation efficiency ( Y 2 ) were used as dependent variables.The formulation variables were optimized by Box-Behnken experimental design.The particle size distribution,PdI,and Zeta potential were measured with a laser particle size analyzer.The microscopic morphology was observed by transmission electron microscopy.The in vitro release rates of Vin-loaded CNs were compared.Results The formulation of Vin-loaded CNs was optimized as follows:chitosan concentration 0.50 mg·mL^-1 ,sodium tripolyphosphate concentration 0.49 mg·mL^-1 ,and stirring time 60 min.The average particle size was 391.6±6.3 nm.The encapsulation efficiency and Zeta potential of Vin-loaded CNs were 77.8 %±1.6 % and 23.2±2.6 mV,respectively.Transmission electron microscopy showed that the Vin-loaded CNs were nearly spherical and the particle size was uniform.The Vin-loaded CNs released slowly in pH 7.4 release media and rat plasma.Conclusion In this study,vinorelbine tartrate was prepared into chitosan nanoparticles with good stability,slow drug release in vitro ,and is expected to improve the drug treatment efficiency.