低临界胶束浓度PEGMA-b-PCL的制备及其药物缓释性能  

Preparation and drug sustained-release properties of PEGMA-b-PCL with low critical micelle concentration

作　　者：周国永 尹付琳 尹城武 王钰杰 陈雨鑫 刘超[1] 成琳 杜海军[1] ZHOU Guoyong;YIN Fulin;YIN Chengwu;WANG Yujie;CHEN Yuxin;LIU Chao;CHENG Lin;DU Haijun(School of Chemical Engineering,Guizhou Minzu University,Guiyang 550025,Guizhou,China;School of Ethnic-Minority Medicine,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 [2]贵州民族大学民族医药学院,贵州贵阳550025

出　　处：《精细化工》2024年第6期1318-1327,共10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)为疏水链段、聚乙二醇甲醚甲基丙烯酸酯(PEGMA)为亲水链段、4-氰基-4-[(十二烷基硫烷基硫代羰基)硫烷基]戊醇(CDPA)为可逆加成-断裂链转移(RAFT)试剂、甲苯为溶剂,在N_(2)氛围、80℃、反应24 h的条件下,通过RAFT聚合法制备了两嵌段共聚物(PEGMA-b-PCL)。将其自组装为胶束,作为纳米药物载体用于负载姜黄素(Cur)。采用FTIR、^(1)HNMR、GPC、SEM、DLS对PEGMA-b-PCL进行了表征,测试了胶束载体的载药和释药性能。结果表明,两嵌段共聚物数均相对分子质量范围为1478~7318,其具有较低的临界胶束浓度(在pH=5.0~7.4,范围为0.920~1.600 mg/L)。胶束载体粒径范围为68.34~186.93 nm。当n(CDPA)∶n(ε-CL)=1∶200时,胶束载药率和包封率最高,可达12.05%±0.29%和75.26%±2.41%。在不同pH环境下,药物缓释性能可达15 d,其中pH=5.0时的累积释药率最高,可达38.20%。Two-block copolymers(PEGMA-b-PCL)were prepared by reversible addition and break chain transfer(RAFT)polymerization of hydrophobicε-caprolactone(ε-CL)and hydrophilic polyethylene glycol methyl ether methacrylate(PEGMA),with 4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanol(CDPA)as RAFT reagent and toluene as solvent under N_(2)atmosphere at 80℃for 24 h.The PEGMA-b-PCL micelles were then formed via self-assembly and used as nanomedical carriers for curcumin(Cur).The PEGMA-b-PCL were characterized by FTIR,^(1)HNMR,GPC,SEM and DLS,and the drug loading and release properties of micelle carriers were analyzed.The results showed that the PEGMA-b-PCL exhibited a number-average relative molecular mass ranging from 1478~7318,and a low critical micelle concentration of 0.920 to 1.600 mg/L at pH=5.0~7.4.The micelle carriers,with a particle size of 68.34~186.93 nm,displayed the highest drug loading and encapsulation rate of 12.05%±0.29%and 75.26%±2.41%,respectively at n(CDPA)∶n(ε-CL)=1∶200.Under different pH conditions,the drug slow-release performance of the micellar carrier could reach 15 d,while the cumulative release rate could reach 38.20%at pH=5.0.

关 键 词：RAFT聚合 两嵌段共聚物 低临界胶束浓度 药物缓释 姜黄素 医药原料 

分 类 号：TQ460.4[化学工程—制药化工]