Yu Lin, Chang Guang Tao, Zhang Huan, Ding Jian Dong
Department of Macromolecular Science, Advanced Materials Laboratory, Fudan University, Shanghai 200433, China.
Int J Pharm. 2008 Feb 4;348(1-2):95-106. doi: 10.1016/j.ijpharm.2007.07.026. Epub 2007 Jul 25.
The paper employs the spontaneous physical gelling property of a biodegradable polymer in water to prepare an injectable sustained release carrier for a PEGylated drug. A series of thermogelling PLGA-PEG-PLGA triblock copolymers were synthesized. The PEGylated camptothecin (CPT) was also prepared and employed as the model of a PEGylated drug, and the solubility of this hydrophobic drug was significantly enhanced to over 150mg/mL. The model drug was completely entrapped into the polymeric hydrogel, and the sustained release lasted for 1 month. The mechanism of the sustained release was diffusion-controlled at the first stage and then was the combination of diffusion and degradation at the late stage. In vivo anti-tumor tests in mice further confirmed the efficacy of the model PEGylated drug released from the hydrogel. This work also revealed the specificity of the PEGylated drug in such a kind of carrier systems by decreasing the critical gelling temperature and increasing the viscosity of the sol. Due to the very convenient drug formulation and highly tunable release rate, an injectable carrier platform for PEGylated drugs is thus set up.
该论文利用一种可生物降解聚合物在水中的自发物理凝胶化特性，制备了一种用于聚乙二醇化药物的可注射缓释载体。合成了一系列热凝胶化的聚乳酸-羟基乙酸共聚物-聚乙二醇-聚乳酸-羟基乙酸共聚物三嵌段共聚物。还制备了聚乙二醇化喜树碱（CPT）并将其用作聚乙二醇化药物的模型，这种疏水性药物的溶解度显著提高到超过150mg/mL。模型药物完全包封在聚合物水凝胶中，缓释持续1个月。缓释机制在第一阶段是扩散控制，后期是扩散和降解的结合。小鼠体内抗肿瘤试验进一步证实了从水凝胶中释放的模型聚乙二醇化药物的疗效。这项工作还通过降低临界凝胶化温度和增加溶胶粘度揭示了聚乙二醇化药物在这种载体系统中的特异性。由于药物制剂非常方便且释放速率高度可调，因此建立了一种用于聚乙二醇化药物的可注射载体平台。
