依托泊苷纳米混合胶束的制备及其理化性质  

Preparation and evaluation of physicochemical properties of etoposide nano-mixed micelles

作　　者：张欣欣 许洁 蒋岩 赵丽艳[1,2] 张万明 ZHANG Xinxin;XU Jie;JIANG Yan;ZHAO Liyan;ZHANG Wanming(School of Pharmacy,Hebei North University,Zhangjiakou,Hebei 075000,China;Hebei Key Laboratory of Neuropharmacology,Zhangjiakou,Hebei 075000,China)

机构地区：[1]河北北方学院药学系,河北张家口075000 [2]河北省神经药理学重点实验室,河北张家口075000

出　　处：《河北科技大学学报》2021年第4期389-399,共11页Journal of Hebei University of Science and Technology

基　　金：国家自然科学基金(81274005);河北省教育厅高校基本科研业务费(JYT2020002);河北省卫生健康委科研基金(20180812)。

摘　　要：为提高依托泊苷制剂的水溶性和稳定性,采用星点设计-效应面法优化依托泊苷纳米混合胶束(ETP mPEG-PLA/P123)的处方工艺。在单因素试验基础上,以投药量、mPEG-PLA所占质量比和水化体积为自变量,以依托泊苷包封率、载药量以及粒径为因变量,进行3因素5水平的星点设计-效应面法实验,采用荧光探针法测定临界胶束浓度(CMC),并对所制备的胶束制剂进行理化性质和释放行为的评估。结果表明,ETP mPEG-PLA/P123胶束制剂的最优处方工艺如下:mPEG-PLA与P123质量比为38∶62,投药量为5 mg,水化体积为6 mL;采用最优处方制得的混合胶束的包封率为87.4%,载药量为4.19%,粒径为115.6 nm,PDI为0.216,Zeta电位为-16.3 mV;荧光探针法测定的CMC值为1.7×10^(-3)g/L,mPEG-PLA/P123胶束稳定性良好;体外释放实验中,依托泊苷可从胶束中缓慢而持续地释放,在48 h内释放量可达80%。采用优化处方制得的ETP mPEG-PLA/P123纳米混合胶束,能显著增加依托泊苷的溶解度,胶束制剂稳定性好,且有一定的缓释作用,可为进一步拓宽依托泊苷新型制剂的应用范围提供理论依据。In order to enhance the aqueous solubility and stability of etoposide preparation,the central composite design-response surface method was used to optimize the prescription technology of etoposide nano-mixed micelles(ETP mPEG-PLA/P123).Based on the results of single factor test,central composite design-response surface method of three factors and five levels was carried out to optimize the prescription technology with drug dosage,the mass ratio of mPEG-PLA and hydration volume as independent variables,and the entrapment efficiency,drug loading and particle size as dependent variables.The critical micelle concentration(CMC)was determined by fluorescence probe method,and the physicochemical properties and release behavior of the prepared micelle preparations were evaluated.The results showed that the optimal prescription of ETP mPEG-PLA/P123 micelle preparation was that mPEG-PLA∶P123=38∶62,the drug dosage was 5 mg,and the hydration volume was 6 mL.After optimization,the entrapment efficiency and drug loading were 87.4% and 4.19%,the particle size was 115.6 nm,PDI was 0.216,and Zeta potential was-16.3 mV.The CMC value was 1.7×10^(-3) g/L,so mPEG-PLA/P123 micelles had high stability.In vitro release experiments,etoposide could be released from micelles slowly and continuously,up to 80%within 48 h.The optimized ETP mPEG-PLA/P123 nano-mixed micelles were able to enormously improve the aqueous solubility of etoposide,and the micelle preparation had good stability and a certain slow-release effect.The results of this study could provide theoretical guidance for further broadening the range of application of new etoposide preparations.

关 键 词：药剂学 依托泊苷 P123 胶束 UPLC 薄膜水化法 星点设计-效应面法 

分 类 号：TQ460.7[化学工程—制药化工] R961[医药卫生—药理学]