星点设计-效应面法优化制备吉非替尼壳聚糖鱼精蛋白纳米粒  

Optimized preparation of gefitinib chitosan protamine nanoparticles by central composite design-response surface method

作　　者：王子臣 赵文明 

机构地区：[1]锦州医科大学药学院,锦州121000

出　　处：《中国新药杂志》2016年第7期807-812,822,共7页Chinese Journal of New Drugs

基　　金：辽宁医学院校长基金(XZJJ20130104-02)

摘　　要：目的:采用星点设计-效应面法优化壳聚糖鱼精蛋白载药纳米粒处方,制备吉非替尼壳聚糖鱼精蛋白纳米粒。方法:以壳聚糖和鱼精蛋白为载体材料,采用离子胶凝法制备吉非替尼壳聚糖鱼精蛋白纳米粒。以包封率和载药量为评价指标,利用Design-Expert 8.0.7 Trial软件对考察因素进行实验设计与结果处理;采用BT-90纳米激光粒度仪测定纳米粒的粒径分布和Zeta电位,透射电镜考察其形态。结果:吉非替尼壳聚糖鱼精蛋白纳米粒的最优处方为:吉非替尼的质量浓度为1 mg·m L-1,壳聚糖的质量浓度为3.5 mg·m L-1,鱼精蛋白的质量浓度为1 mg·m L-1。此处方所得壳聚糖鱼精蛋白载药纳米粒的包封率和载药量分别为87.34%和19.55%,实际观测值与模型预测值相差不大,模型具有很好的预测性。平均粒径为169 nm,分散指数PDI值为0.059,Zeta电位为+24.7 m V,透射电镜显示纳米粒为球形或类球形,结构完整,大小均一,稳定。结论:星点设计-效应面法能准确可靠的优化吉非替尼壳聚糖鱼精蛋白纳米粒的制备处方,所建立的数学模型具有较好的预测能力和实用性。Objective： To optimize the formulation of drug-loaded chitosan protamine nanoparticles by the central composite design-response surface method, and to prepare the gefitinib chitosan protamine nanoparticles. Methods： Using chitosan and protamine as the main carriers, the gefitinib chitosan protamine nanoparticles were prepared by adopting ionic gelation method. The design and result assessment were carried out with Design-Expert 8.0.7 Trial software using encapsulation efficiency and drug loading as indices. The particle size distribution and the Zeta potential of the nanoparticles were measured by BT-90 nano laser particle size analyzer. The nanoparticles morphology was observed by transmission electron microscopy. Results： The best formulation of gefitinib chitosan protamine nanoparticles was 1 mg·mL^-1 gefitinib, 3.5 mg·mL^-1 chitosan and 1 mg·mL^-1 protamine. Encapsula- tion efficiency and drug loading of the drug-loaded chitosan protamine nanoparticles were 87.34% and 19.55% , respectively, under the optimal formulation. The difference between the actual observation value and predicted val- ue by the model had no significant difference, indicating a good prediction of the model. The average particle size was 169 nm. The PDI value was 0. 059 and the Zeta potential was ＋24.7 mV. From the transmission electron mi- croscopic results, the nanoparticles were spherical, their structure was complete, and their size was uniform and stable. Conclusion ： The optimized formulation of the gefitinib chitosan protamine nanoparticles can be obtained ac- curately and reliably by the central composite design-response surface method. The mathematical model developed in this study has been proved to be predictable and feasible.

关 键 词：星点设计-效应面法 吉非替尼 壳聚糖纳米粒 鱼精蛋白 

分 类 号：R944[医药卫生—药剂学]