星点设计-效应面法优化载羟基喜树碱PGPP纳米粒的制备工艺  

Optimization on preparation of glycyrrhetinic acid modified PEG-pep-PEI-PLGA nanoparticles loaded with hydroxycamptothecin by central composite design-response surface method

作　　者：刘萍 蒋志健 张杰祥 赵瑞芝[2] 胡巧红 LIU Ping;JIANG Zhijian;ZHANG Jiexiang;ZHAO Ruizhi;HU Qiaohong(School of Pharmacy,Guangdong Pharmaceutical University,Guangzhou 510006,China;The Second Clinical College,Guangzhou University of Traditional Chinese Medicine,Guangzhou 510006,China)

机构地区：[1]广东药科大学药学院,广东广州510006 [2]广州中医药大学第二临床医学院,广东广州510006

出　　处：《广东药科大学学报》2018年第1期1-6,共6页Journal of Guangdong Pharmaceutical University

基　　金：广东省科技计划项目(2017A020211013)

摘　　要：目的制备载羟基喜树碱(HCPT)的甘草次酸修饰的PEG-pep-PEI-PLGA(PGPP)纳米粒。方法采用乳化-溶剂挥发法制备HCPT/PGPP纳米粒,应用单因素法考察超声功率、投药量、超声时间以及水相∶油相体积比对栽药纳米粒包封率和载药量的影响。在此基础上,应用星点设计-效应面法,以超声功率、投药量及水相∶油相体积比为考察因素,以包封率和载药量为考察指标,优化载药纳米粒制备工艺并进行验证。结果超声功率对包封率有显著影响,投药量对载药量的影响较为明显。优化获得的HCPT/PGPP纳米粒制备工艺为:水相∶油相为10.8∶1(体积比),超声功率为494 W,投药量为0.82 mg。该工艺制备的载药纳米粒包封率为(81.2±2.7)%,载药量为(3.76±0.13)%,Zeta电位为(27.4±3)m V,平均粒径为[(331.9±10.5)nm](PDI=0.289±0.024)。结论乳化-溶剂挥发法适用于制备HCPT/PGPP纳米粒,星点设计-效应面法可优化获得载药纳米粒的最佳制备工艺,所得的载药纳米粒包封率和载药量较高,粒径较均匀且稳定性好。Objective To prepare glycyrrhetinic acid modified PEG-pep-PEI-PLGA(PGPP)nanoparticles loaded with hydroxycamptothecin(HCPT).Methods HCPT/PGPP nanoparticles were prepared by emulsifying-solvent evaporation method.The influence of the ultrasonic power,ultrasonic time,drug dosage and water phase/oil phase volume ratio on the entrapment efficiency and drug loading capacity of HCPT/PGPP nanoparticles were investigated respectively.With the entrapment efficiency and drug loading capacity as the indexes,the preparation process of HCPT/PGPP nanoparticles was optimized by central composite design-response surface methodology and validated.Results The ultrasonic power had significant influence on the encapsulation efficiency,and the drug dosage had obvious influence on the drug loading capacity.The optimal preparation process of HCPT/PGPP nanoparticles was as follows:water phase/oil phase volume ratio of10.8∶1,ultrasonic power of494W,the drug dosage of0.82mg.The entrapment efficiency,drug loading capacity of the HCPT/PGPP nanoparticles prepared by the optimal process were(81.2±2.7)%and(3.76±0.13)%,respectively,with Zeta potential of(27.4±3)mV,average particle size of(331.9±10.5)nm and polydispersity index of(0.289±0.024).Conclusion The emulsifying-solvent evaporation method is feasible to prepare HCPT/PGPP nanoparticles.The central composite design-response surface methodology is suitable for optimizing the preparation process of HCPT/PGPP nanoparticles with high entrapment efficiency and drug loading capacity,uniform particle size and high stability.

关 键 词：羟基喜树碱/PGPP纳米粒 星点设计-效应面法 工艺优化 乳化-溶剂挥发法 

分 类 号：R944.4[医药卫生—药剂学]