Injectable block copolymer hydrogels for sustained release of a PEGylated drug
Injectable block copolymer hydrogels for sustained release of a PEGylated drug
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用于持续释放聚乙二醇化药物的可注射嵌段共聚物水凝胶
DOI：
10.1016/j.ijpharm.2007.07.026
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发表时间：
2008-02-04
影响因子：
5.8
通讯作者：
Ding, Jian Dong
中科院分区：
文献类型：
--
作者：
Yu, Lin;Chang, Guang Tao;Ding, Jian Dong
本文利用可生物降解聚合物在水中的自发物理凝胶性，制备了聚乙二醇化药物的可注射缓释载体。合成了一系列热凝胶PLGA-PEG-PLGA三嵌段共聚物。还制备了聚乙二醇化喜树碱(CPT)，并将其作为聚乙二醇化药物的模型，使该疏水药物的溶解度显著提高到150 mg/mL以上。模型药物完全包埋在聚合物水凝胶中，缓释时间为1个月。缓释机制在初期为扩散控制，后期为扩散与降解相结合。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有效性。这项工作还揭示了聚乙二醇化药物在这样的载体体系中通过降低临界凝胶温度和增加溶胶的粘度来实现药物的专一性。由于药物处方非常方便，释放速度非常可调，因此建立了聚乙二醇化药物的注射载体平台。(C)2007爱思唯尔B.V保留所有权利。
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 150 mg/mL. The model drug was completely entrapped into the polymeric hydrogel, and the sustained release lasted for I 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. (c) 2007 Elsevier B.V All rights reserved.