Matrix metalloproteinase-sensitive thermogelling polymer for bioresponsive local drug delivery.
Matrix metalloproteinase-sensitive thermogelling polymer for bioresponsive local drug delivery.
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DOI：
10.1016/j.actbio.2011.02.005
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发表时间：
2011-05
影响因子：
9.7
通讯作者：
Jo, Seongbong
中科院分区：
文献类型：
--
作者：
Garripelli, Vivek Kumar;Kim, Jin-Ki;Son, Sejin;Kim, Won Jong;Repka, Michael A.;Jo, Seongbong
一个成功的生物反应性药物传递系统的开发需要精细的材料工程，使它们能够响应来自生理环境的信号。在这项研究中，我们提出了一种新的基于Pluronic®的热凝胶体系，该体系含有基质金属蛋白酶-2 （MMP2）响应肽序列。以Pluronic®三嵌段共聚物为原料合成了一种新型热敏多嵌段共聚物，该共聚物含有mmp2不稳定的八肽（Gly-Pro-Val-Gly-Leu-Ile-Gly-Lys）。该聚合物被设计成在体温下形成热凝胶，并在肿瘤中过度表达的MMP存在下降解。合成的聚合物是多嵌段共聚物，含有~ 2.5个单位的Pluronic®。多嵌段共聚物溶液在体温附近表现出逆热凝胶。在特定浓度下，多嵌段共聚物溶液的凝胶温度低于相应的Pluronic®单体。合成的聚合物的细胞毒性较单体低。疏水抗癌药物紫杉醇在聚合物溶液中的溶解度通过胶束形成而提高。合成的聚合物在MMP的存在下优先降解。紫杉醇释放量与酶浓度有关。这些结果表明，合成的聚合物由于其独特的相变和生物反应行为，具有作为受控药物递送系统的潜力。
Development of a successful bioresponsive drug delivery system requires exquisite engineering of materials so that they are able to respond to the signals stemming from the physiological environment. In this study, we proposed a new Pluronic® based thermogelling system containing matrix metalloproteinase-2 (MMP2) responsive peptide sequences. A novel thermosensitive multiblock copolymer comprising an MMP2-labile octapeptide (Gly-Pro-Val-Gly-Leu-Ile-Gly-Lys) was synthesized from Pluronic® triblock copolymer. The polymer was designed to form thermogel at body temperature and degrade in presence of MMP overexpressed in the tumor. The synthesized polymer was a multiblock copolymer with ~ 2.5 units of Pluronic®. The multiblock copolymer solutions exhibited a reverse thermal gelation around body temperature. The gelation temperatures of the multiblock copolymer solutions were lower than those of the corresponding Pluronic® monomer at a particular concentration. The cytotoxicity of the synthesized polymer was lower comparing to its monomer. The solubility of hydrophobic anticancer drug, paclitaxel, was enhanced in the polymer solutions via micelle formation. The synthesized polymer was preferentially degraded in presence of MMP. Paclitaxel release was dependent on the enzyme concentration. These findings suggest that the synthesized polymer has the potential as controlled drug delivery system due to its unique phase transition and bioresponsive behavior.
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