Arslan Mehmet, Aydin Duygu, Degirmenci Aysun, Sanyal Amitav, Sanyal Rana
Department of Chemistry, Bogazici University, Bebek, Istanbul 34342, Turkey.
Center for Life Sciences and Technologies, Bogazici University, Istanbul 34342, Turkey.
ACS Omega. 2017 Oct 12;2(10):6658-6667. doi: 10.1021/acsomega.7b00787. eCollection 2017 Oct 31.
Design, synthesis, and application of cyclodextrin (CD) containing thermoresponsive hydrogels fabricated from thiol-reactive telechelic polymers are reported. Hydrophilic polymers containing 2-hydroxyethyl methacrylate and/or di(ethylene glycol)methylether methacrylate monomers as side chains and thiol-reactive groups at chain ends were synthesized. A series of hydrogels was fabricated using thiol-ene conjugation of these thiol-reactive polymers with multivalent thiol-containing CDs as crosslinkers. Clear and transparent hydrogels were obtained with good conversion (79-89%) by utilizing the "nucleophilic" and "radical" thiol-ene "click" reactions. Analysis of the amount of residual thiol groups in these hydrogels using Ellman's reagent suggested that gels with a moderately well-defined network structure were obtained. Hydrogels fabricated using different telechelic polymers were examined for their properties such as morphology, equilibrium water uptake, and rheological characteristics. Cytocompatibility of these hydrogels was ascertained by a cell viability assay that demonstrated low toxicity toward fibroblast cells. Thereafter, the CD-containing hydrogels were evaluated for the loading and controlled release of puerarin, an antiglaucoma drug. Utilization of thermoresponsive polymers as the matrix for these hydrogels allows use of temperature as a stimulus to modulate the drug release. A slower and more sustained drug release was observed at physiological temperatures compared to ambient conditions. The effect of temperature on the elasticity of the hydrogel was investigated rheologically to demonstrate that the collapse of the network structure occurs near physiological temperatures. The increased hydrophobicity and compactness of the gel matrix at higher temperatures results in a slower drug release. The strategy employed here demonstrates that tuning the matrix composition of hydrogels with well-defined network structures through appropriate choice of responsive copolymers allows design of materials with control of their physical properties and drug-release behavior.
报道了由硫醇反应性遥爪聚合物制备的含环糊精（CD）的热响应水凝胶的设计、合成及应用。合成了以甲基丙烯酸2-羟乙酯和/或甲基丙烯酸二（乙二醇）甲醚为侧链且链端含有硫醇反应性基团的亲水性聚合物。使用这些硫醇反应性聚合物与多价含硫醇CD进行硫醇-烯共轭反应制备了一系列水凝胶作为交联剂。通过利用“亲核”和“自由基”硫醇-烯“点击”反应，获得了具有良好转化率（79-89%）的透明水凝胶。使用埃尔曼试剂分析这些水凝胶中残留硫醇基团的量表明，获得了具有适度明确网络结构的凝胶。研究了使用不同遥爪聚合物制备的水凝胶的形态、平衡吸水率和流变特性等性质。通过细胞活力测定确定了这些水凝胶的细胞相容性，结果表明其对成纤维细胞的毒性较低。此后，评估了含CD水凝胶对抗青光眼药物葛根素的负载和控释性能。使用热响应聚合物作为这些水凝胶的基质使得能够利用温度作为刺激来调节药物释放。与环境条件相比，在生理温度下观察到药物释放更缓慢且更持久。通过流变学研究了温度对水凝胶弹性的影响，以证明网络结构在接近生理温度时发生塌陷。较高温度下凝胶基质疏水性和致密性的增加导致药物释放更缓慢。这里采用的策略表明，通过适当选择响应性共聚物来调节具有明确网络结构的水凝胶的基质组成，可以设计出能够控制其物理性质和药物释放行为的材料。
