Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
Biomacromolecules. 2010 Aug 9;11(8):2143-51. doi: 10.1021/bm100514p.
Photopolymerized thermosensitive A-B-A triblock copolymer hydrogels composed of poly(N-(2-hydroxypropyl)methacrylamide lactate) A-blocks, partly derivatized with methacrylate groups to different extents (10, 20, and 30%) and hydrophilic poly(ethylene glycol) B-blocks of different molecular weights (4, 10, and 20 kDa) were synthesized. The aim of the present study was to correlate the polymer architecture with the hydrogel properties, particularly rheological, swelling, degradation properties and release behavior. It was found that an increasing methacrylation extent and a decreasing PEG molecular weight resulted in increasing gel strength and cross-link density, which tailored the degradation profiles from 25 to more than 300 days. Polymers having small PEG blocks showed a remarkable phase separation into polymer- and water-rich domains, as demonstrated by confocal microscopy. Depending on the hydrophobic domain density, the loaded protein resides in the hydrophilic pores or is partitioned into hydrophilic and hydrophobic domains, and its release from these compartments is tailored by the extent of methacrylation and by PEG length, respectively. As the mechanical properties, degradation, and release profiles can be fully controlled by polymer design and concentration, these hydrogels are suitable for controlled protein release.
由聚（N-（2-羟丙基）甲基丙烯酰胺乳酸酯）A 嵌段和不同程度（10、20 和 30%）部分衍生的甲基丙烯酰基的部分和不同分子量的亲水性聚（乙二醇）B 嵌段（4、10 和 20 kDa）组成的光聚合热敏 A-B-A 三嵌段共聚物水凝胶被合成。本研究的目的是将聚合物结构与水凝胶性质相关联，特别是流变学、溶胀、降解特性和释放行为。结果发现，随着甲基丙烯酰化程度的增加和 PEG 分子量的降低，凝胶强度和交联密度增加，从而将降解曲线从 25 天调整到 300 天以上。具有小 PEG 块的聚合物表现出明显的相分离为聚合物和富含水的区域，如共聚焦显微镜所示。根据疏水区密度，负载的蛋白质存在于亲水孔中或分配到亲水和疏水区域中，并且其从这些隔室中的释放分别通过甲基丙烯酰化程度和 PEG 长度进行调节。由于机械性能、降解和释放曲线可以通过聚合物设计和浓度完全控制，因此这些水凝胶适合于控制蛋白质释放。
