Drapala Pawel W, Brey Eric M, Mieler William F, Venerus David C, Kang Derwent Jennifer J, Pérez-Luna Victor H
a Department of Chemical and Biological Engineering, Illinois Institute of Technology, 10 W. 33rd Street, Chicago, IL 60616-3793, USA.
J Biomater Sci Polym Ed. 2011;22(1-3):59-75. doi: 10.1163/092050609X12578498952315.
Thermo-responsive hydrogels have shown promise as injectable materials for local drug delivery. However, the phase-induced changes in polymer properties of N-isopropylacrylamide (NIPAAm) can pose additional challenges for achieving controlled protein release. In this work, thermo-responsive hydrogels derived from NIPAAm and cross-linked with poly(ethylene glycol) diacrylate (PEG-DA) were synthesized via free radical polymerization. The volume phase transition temperature (VPTT) of the hydrogels ranged from 32.9°C to 35.9°C. Below the VPTT, swelling ratios of the hydrogels decreased with cross-linker concentration, and showed a sharp drop (at least 4-fold) upon phase change. Protein encapsulation efficiency was high (84-90%) and decreased with cross-linker concentration. Release of bovine serum albumin, a model protein, at body temperature was significantly higher than at room temperature (67% at 37°C compared to 44% at 23°C after 48 h). The release kinetics of proteins from the hydrogels were initially expected to be a function of cross-link density. However, at the hydrogel compositions explored in this work, protein release did not change significantly with cross-linker mol fraction. The thermo-responsive hydrogels offer a promising platform for the localized delivery of proteins.
热响应水凝胶已显示出有望作为用于局部药物递送的可注射材料。然而，N-异丙基丙烯酰胺（NIPAAm）聚合物性质的相诱导变化可能给实现可控的蛋白质释放带来额外挑战。在这项工作中，通过自由基聚合合成了由NIPAAm衍生并与聚（乙二醇）二丙烯酸酯（PEG-DA）交联的热响应水凝胶。水凝胶的体积相变温度（VPTT）范围为32.9°C至35.9°C。在VPTT以下，水凝胶的溶胀率随交联剂浓度降低，并在相变时呈现急剧下降（至少4倍）。蛋白质包封效率很高（84-90%），并随交联剂浓度降低。作为模型蛋白质的牛血清白蛋白在体温下的释放明显高于室温（48小时后，37°C时为67%，而23°C时为44%）。最初预计蛋白质从水凝胶中的释放动力学是交联密度的函数。然而，在这项工作中探索的水凝胶组成下，蛋白质释放并未随交联剂摩尔分数而显著变化。热响应水凝胶为蛋白质的局部递送提供了一个有前景的平台。
