Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China.
Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, PR China.
Int J Pharm. 2014 Oct 20;474(1-2):232-40. doi: 10.1016/j.ijpharm.2014.08.018. Epub 2014 Aug 19.
A cyclodextrin-containing pH-responsive star polymer, with cyclodextrin polymer and pH-sensitive poly(2-(dimethylamino)ethyl methacrylate) as the core and poly(ethylene glycol) as the arm, was evaluated as drug carriers in vitro and in vivo. Doxorubicin (DOX) was successfully loaded into the star polymer to form nanoparticles (DOX-NPs) via host-guest interaction. The physicochemical properties such as drug loading content, size, morphology, stability and physical state of DOX-NPs were characterized in detail by (1)H NMR, DLS, SEM and DSC. Uniform and stable DOX-NPs with high encapsulation efficiency of 77.1% were obtained, and they also exhibited sustainable and controllable release of DOX in vitro. The cellular uptake of DOX-NPs was in concentration-, time- and cell type-dependent manners, and the cytotoxicity of DOX-NPs was significantly high toward HeLa and HepG2 cancer cells. Furthermore, in vivo anti-tumor experiment on BALB/c mice bearing cervical tumor showed that DOX-NPs could effectively suppress the growth of tumor without significant side effect. These findings suggest that the cyclodextrin-containing pH-responsive star polymer has a promising potential in developing novel drug delivery system for cancer therapy.
一种含环糊精的 pH 响应星型聚合物，以环糊精聚合物和 pH 敏感的聚 2-（二甲氨基）乙基甲基丙烯酸酯为核，聚乙二醇为臂，被评估为体外和体内的药物载体。通过主客体相互作用，阿霉素（DOX）成功地负载到星型聚合物中形成纳米颗粒（DOX-NPs）。通过 1H NMR、DLS、SEM 和 DSC 详细表征了 DOX-NPs 的物理化学性质，如载药量、粒径、形态、稳定性和物理状态。得到了均匀稳定的 DOX-NPs，包封率高达 77.1%，并且在体外具有可持续和可控的 DOX 释放。DOX-NPs 的细胞摄取具有浓度、时间和细胞类型依赖性，并且对宫颈癌 HeLa 和 HepG2 癌细胞的细胞毒性显著较高。此外，在携带宫颈肿瘤的 BALB/c 小鼠体内抗肿瘤实验表明，DOX-NPs 能够有效抑制肿瘤生长，而没有明显的副作用。这些发现表明，含环糊精的 pH 响应星型聚合物在开发用于癌症治疗的新型药物传递系统方面具有广阔的应用前景。
