一种两亲性嵌段共聚物胶束的制备及其对叶酸的负载和控制释放

PREPARATION OF MICELLES FROM AN AMPHIPHILIC BLOCK COPOLYMER AND THEIR LOADING AND CONTROLLED RELEASE OF FOLIC ACID

采用可逆加成-断裂链转移(RAFT)聚合合成了以丙烯酸异丁酯(IBA)、甲基丙烯酸2-二甲氨乙酯(DMAEMA)无规共聚嵌段与聚丙烯酸-2-羟丙酯(PHPA)组成的两亲性两嵌段共聚物(P(IBA-co-DMAEMA)-b-PHPA),并用凝胶渗透色谱(GPC)、核磁共振波谱(1 H-NMR)及红外光谱(FTIR)对其进行了结构和组成表征.这种共聚物在水溶液介质下能够自组装形成稳定的聚合物胶束,通过荧光探针技术测得其低临界胶束浓度(CMC)约为2.1 mg/L.透射电镜(TEM)和动态激光光散射(DLS)测定结果表明,P(IBA-co-DMAEMA)-b-PHPA在水溶液中自组装形成的胶束呈球形核壳结构,其平均动力学直径处于110～136 nm之间,且呈均匀较窄分布.以该聚合物胶束为载体、叶酸(FA)为模型药物,模拟人体生理环境进行药物体外释放研究.结果表明,叶酸负载量及负载效率分别高达38%和76%.在温度37℃、离子强度I=0.15 mol/kg、pH值分别为2.0、7.4、9.2磷酸缓冲溶液(PBS)下,FA在40 h内的释放都相对较快,释放速率随pH的增加依次增大.随后释放变缓,最大累积释放率分别为36%,61%和80%.

A novel of amphiphilic diblock copolymer（P（IBA-co-DMAEMA）-b-PHPA）,which composed of poly（isobutyl acrylate-co-2-（N,N-dimethylamino）ethyl methacrylate） random copolymer block and poly（2-hydroxypropyl acrylate）,was synthesized by reversible addition-fragmentation chain transfer（RAFT） polymerization,and its structure and composition were confirmed by gel permeation chromatography（GPC）,1H nuclear magnetic resonance（1H-NMR） spectroscopy and FTIR spectroscopy.This copolymer could self-assemble into stable polymeric micelles.The critical micelle concentration values of the self-assembled micelles were about 2.1 mg/L in distilled water relying on fluorescent probe technique.The results measured by dynamic light scattering（DLS） and transmission electron microscopy（TEM） showed that the self-assembled P（IBA-co-DMAEMA）-b-PHPA micelles exhibited spherical core-shell structure with mean hydrodynamic diameter around 110~136 nm and uniform and narrow size distribution in aqueous media.The model drug folic acid（FA） was loaded into the micelles as drug carrier material and the in vitro drug release behavior was investigated at physiological conditions.We found that the FA-loaded content and the entrapment efficiency reached up to 38% and 76%,respectively.In phosphate buffer solution（PBS）at ionic strength I=0.15 kg/mol,temperatures T=37℃,and different pH=2.0,7.4 and 9.2,in vitro release rates of folic acid（FA） from polymeric micelles were all relatively faster within 40 h,and increased with pH value increase.Followed by slow release,the largest accumulation release percentage was 36%,61% and 80%,respectively.Thus,the polymeric micelles are expected to be a novel type of carrier material with pH-responsive and high drug loading capacity for drug delivery.