pH敏感两亲性嵌段共聚物胶束的制备及其负载紫杉醇体外药效的研究

Preparation and in vitro Anti-cancer Effect of Paclitaxel-loaded p H-sensitive Amphiphilic Block Copolymer Micelles

采用可逆加成-断裂链转移(RAFT)聚合法,以丙烯酸(AA)、丙烯酸异丁酯(IBA)无规共聚物与聚丙烯酸-2-羟丙酯(PHPA)反应,制备了具有pH敏感性的两亲性嵌段共聚物(P(IBA-co-AA)-b-PHPA).用红外光谱(FTIR)、核磁共振(1H-NMR)、凝胶渗透色谱(GPC)对其结构进行表征.此共聚物在水溶液中可自组装形成胶束,临界胶束浓度约为2.0mg/L.由透射电子显微镜(TEM)、动态光散射(DLS)表征可知胶束为尺寸约100nm的球形颗粒;用DLS观察到胶束粒径随pH值的升高而逐渐增大.以抗癌药物紫杉醇为模型药物,研究载药胶束在模拟人体环境中的控释行为.用CellCountingKit-8(简称CCK-8)法分别研究聚合物胶束对MCF-7人乳腺癌细胞和A549人肺癌细胞的细胞毒性,并评价载药胶束在两细胞中的抗癌效果.结果表明,P(IBA-co-AA)-b-PHPA可作为包载紫杉醇的一种新型纳米材料,载药胶束的体外释放呈明显pH依赖性,且具有较好的体外抗肿瘤活性,有望成为理想的抗肿瘤药物载体.

A novel of p H-sensitive amphiphilic block copolymer poly（ isobutyl acrylate-co-crylic acid）-b-poly-（ 2-hydroxypropyl acrylate）（ P（ IBA-co-AA）-b-PHPA） was synthesized by reversible addition fragmentation chain transfer radical（ RAFT） polymerization. The block copolymer was characterized by Fourier transform infrared spectroscopy（ FTIR）,1H nuclear magnetic resonance（1H-NMR） and gel permeation chromatography（ GPC）. Nanosized micelles were formed by self-assembly when the P（ IBA-co-AA）-b-PHPA was dissolved in water solution,the critical micelle concentration value was about 2. 0 mg / L. These nanosized micelles were characterized by transmission electron microscopy（ TEM） and dynamic light scattering（ DLS）. The assembled micelles were regularly spherical in the shape with an average size of ca. 100 nm. The diameters of the micelles increased with increasing the p H values were studied by DLS. The drug delivery behaviors of the micelles embedding anti-cancer drug paclitexel（ PTX） in a simulated human body environment were studied. The Cell Counting Kit-8 assay（ CCK-8） was used to evaluate cytotoxicity of the polymeric micelles. The in vitro antitumor activity was evaluated in human breast carcinoma cell line MCF-7 and human lung adenocarcinoma cell line A-549,then the nanosized micelles used as the carrier of the paclitaxel（ PTX） were studied. The in vitro antitumor activity was evaluated in MCF-7 cells and A-549 cells. The results showed that P（ IBA-co-AA）-b-PHPA micelles exhibited p H-sensitive behavior because of the presence of AA in the feed. The amphiphilic block copolymer P（ IBA-co-AA）-b-PHPA was one of novel and ideal biomaterials as PTX nano-carrier,PTXloaded micelles presented sustained release profiles and achieved higher anti-tumor activity. It was a promising anti-cancer drug carrier.