星点设计效应面法优化一氧化氮供体型姜黄素胶束的制备工艺  

Optimization of the process for the preparation of curcumin micelle modified by nitric oxide donor by star-point design-response surface method

作　　者：钟荣生 饶小勇[1,3] 房元英 何雁[1] 陆浩伟 刘微[1,3] 罗晓健[1,3] ZHONG Rongsheng;RAO Xiaoyong;FANG Yuanying;HE Yan;LU Haowei;LIU Wei;LUO Xiaojian(Jiangxi University of Chinese Medicine,Nanchang 330004,China;Affiliated Hospital of Jiangxi University of Chinese Medicine,Nanchang 330006,China;National Engineering Research Center for Chinese Medicine Solid Preparation Manufacturing Technology,Nanchang 330006,China)

机构地区：[1]江西中医药大学,南昌330004 [2]江西中医药大学附属医院,南昌330006 [3]中药固体制剂制造技术国家工程研究中心,南昌330006

出　　处：《西北药学杂志》2023年第1期107-112,共6页Northwest Pharmaceutical Journal

基　　金：江西省卫生健康委科技计划项目(编号:202131041);江西省中医药科技计划一般项目(编号:2020A0356);江西省主要学科和技术带头人培养计划——领军人才项目(编号:20204BCJ22032);江西省教育厅科学技术研究项目(编号:GJJ211209)。

摘　　要：目的采用星点设计效应面法优化一氧化氮(NO)供体型姜黄素胶束(curcumin micelle modified by nitric oxide donor,Cur-PLA-NO)的处方及工艺。方法以粒径、质量浓度及电位为评价指标,优化Cur-PLA-NO的制备处方及工艺,并对Cur-PLA-NO进行体外释放行为的评价;以bEnd.3细胞为体外血脑屏障模型,评价胶束递药系统协助姜黄素(curcumin,Cur)透过血脑屏障(blood-brain barrier,BBB)的能力。结果确定Cur-PLA-NO的最优处方:胶束聚合物(mPEG-PLA-NO)和聚乙二醇-12-羟基硬脂酸酯(polyoxyl 15 hydroxystearate,HS15)以质量比为8∶6加入适量溶剂叔丁醇中,于60℃以500 r·min^(-1)磁力搅拌1 h,加入质量浓度1 mg·mL^(-1)冻干保护剂甘露醇,冻干后即得。依此条件制备的Cur-PLA-NO质量浓度为0.702 mg·mL^(-1),平均粒径为(26.41±0.35)nm,多聚分散系数(polymerdispersityindex,PDI)为0.23±0.005,Zeta电位为(-13.25±0.35)mV;体外释放结果表明,Cur-PLA-NO中Cur的释放符合一级动力学方程,无突释现象并缓慢释放;Cur溶液和Cur-PLA-NO中Cur透过BBB的百分率分别为27.5%±0.003%、42.2%±0.003%。结论依据星点设计效应面法优选的Cur-PLA-NO胶束,粒径可控、载药量高,呈现负电荷特性,且Cur-PLA-NO的构建能显著提高Cur透过BBB的能力。Objective To optimize curcumin micelle modified by nitric oxide donor(Cur-PLA-NO)prescription and process by using star-point design-response surface method.Methods The preparation prescription and process of Cur-PLA-NO were optimized by using particle size,content and potential as evaluation indexes.The in vitro release behavior of Cur-PLA-NO was evaluated.The ability of the micellar drug delivery system to assist curcumin(Cur)to cross the blood-brain barrier(BBB)was evaluated using bEnd.3 cells as an in vitro BBB model.Results The optimal prescription of Cur-PLA-NO was determined as follows:micelle polymer(mPEG-PLA-NO)and polyoxyl 15 hydroxystearate(HS15)were added to an appropriate amount of solvent tert-butanol at a mass ratio of 8∶6,stirred magnetically at 60℃,500 r·min^(-1)for 1 hour,and lyophilized by adding 1 mg·mL^(-1)lyophilized protective agent mannitol.The Cur-PLA-NO prepared under these conditions had a content of 0.702 mg·mL^(-1),a mean particle size of(26.41±0.35)nm,polymer dispersity index(PDI)of 0.23±0.005,and a Zeta potential of(-13.25±0.35)mV.The in vitro release results showed that the release of Cur from Cur-PLA-NO was in accordance with the first-order kinetic equation,without sudden release and slow release.The percentages of Cur crossing the BBB in Cur solution and Cur-PLA-NO were 27.5%±0.003%and 42.2%±0.003%,respectively.Conclusion The Cur-PLA-NO micelles were optimized based on the star-point design-response surface method,with controllable particle size,high drug loading,and negative charge characteristics,and the construction of Cur-PLA-NO significantly increased the ability of Cur to cross the BBB.

关 键 词：姜黄素 胶束 星点设计效应面法 血脑屏障 

分 类 号：R94[医药卫生—药剂学]