低CMC纳米载体PEGMA-b-PLLA-b-PCL的制备及其药物缓释性能  

Preparation and drug sustained release performance of low CMC nanocarrier PEGMA-b-PLLA-b-PCL

作　　者：尹付琳 刘超[1] 陈雨鑫 尹城武 杜海军[1] 周国永 YIN Fulin;LIU Chao;CHEN Yuxin;YIN Chengwu;DU Haijun;ZHOU Guoyong(School of Chemical Engineering,Guizhou Minzu University,Guiyang 550025,Guizhou,China)

机构地区：[1]贵州民族大学化学工程学院,贵州贵阳550025

出　　处：《精细化工》2023年第11期2503-2515,2521,共14页Fine Chemicals

基　　金：国家自然科学基金项目(82060714);贵州省省级科技计划项目(黔科合基础-ZK[2022]一般216);贵州省高等学校绿色化学与资源环境创新团队项目(黔科技[2022]13号);贵州民族大学科研项目(GZMUZK[2021]YB09)。

摘　　要：以ε-己内酯(ε-CL)为疏水原料、聚乙二醇甲醚甲基丙烯酸酯(PEGMA)为亲水原料、以L-丙交酯(LLA)为亲疏水性过渡原料、4-氰基-4-[(十二烷基磺胺基硫代羰基)磺胺基]戊醇(CDPA)为引发剂,利用可逆加成-断裂链转移法制备了超低临界胶束浓度(CMC)的聚乙二醇甲醚甲基丙烯酸酯-聚丙交酯-聚己内酯(PEGMA-b-PLLA-b-PCL)。通过FTIR、1HNMR、GPC、DLS和SEM对聚合物的结构、相对分子质量及粒径进行了测定,用界面张力法测得了PEGMA-b-PLLA-b-PCL胶束溶液的CMC,用溶剂挥发法负载姜黄素(CUR)制备了载药胶束溶液,并计算了其载药量和包封率,进一步考察了载药胶束溶液在不同环境下的释药能力。结果表明,聚合物相对分子质量为1220~8782,粒径为28~180 nm,且最低CMC为0.62μg/m L(pH=7.4)。当n(CDPA)∶n(LLA)=1∶200、n(PEGMA)∶n(PCL)=1∶4时制得的PEGMA1-b-PLLA-b-PCL4载药胶束的载药量和包封率最高,可达17.3%和79.4%(p H=7.4),且药物释放可在15 d内完成,在p H=5.0环境下累积释药量最高,可达45.53%。Poly(ethylene glycol)methyl ether methacrylate-b-poly(L-lactide)-b-poly(ε-caprolactone)(PEGMA-b-PLLA-b-PCL)with ultra-low critical micellar concentration(CMC)was prepared by reversible addition-fragmentation chain transfer method usingε-caprolactone(ε-CL)as hydrophobic material,poly(ethylene glycol)methyl ether methacrylate(PEGMA)as hydrophilic material,L-lactide(LLA)as hydrophilic and hydrophobic transition material,and 4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanol(CDPA)as initiator.The structure,relative molecular mass and particle size of the polymer obtained were analyzed by FTIR,1HNMR,GPC,DLS and SEM,while the CMC was measured by interstitial-tension method.Curcumin was loaded into the micelle via solvent volatilization method,and the drug-loaded micelle prepared was analyzed for its drug-loading capability,encapsulation efficiency and the drug release performance in different environments.The results showed that the polymers obtained exhibited relative molecular mass ranging from 1220 to 8782,particle size from 28 to 180 nm,and the lowest CMC of 0.62μg/mL(pH=7.4).The PEGMA1-b-PLLA-b-PCL4 with n(CDPA)∶n(LLA)=1∶200,n(PEGMA)∶n(PCL)=1∶4 displayed the highest drug-loading capability and encapsulation efficiency,17.3%and 79.4%(pH=7.4)respectively.Moreover,the drug release could be completed within 15 d,with the highest cumulative drug release of 45.53%at pH=5.0.

关 键 词：可逆加成-断裂链转移 低CMC 纳米载体 姜黄素 缓释 医药原料 

分 类 号：TQ460.4[化学工程—制药化工]