Uchiyama Tomoaki, Kiritoshi Yoshihiro, Watanabe Junji, Ishihara Kazuhiko
Department of Materials Engineering, School of Engineering, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Biomaterials. 2003 Dec;24(28):5183-90. doi: 10.1016/s0142-9612(03)00441-1.
The purpose of this study is to ascertain the applicable possibility of H(2)O(2) degradable hydrogel for fabrication of insulin release system synchronized with the change in the glucose concentration in the medium. The hydrogel was prepared by using 2-methacryloyloxyethyl phosphorylcholine (MPC) and crosslinker. The favorable characteristic of the hydrogel was H(2)O(2) concentration responsive degradation. The H(2)O(2) was utilized and produced by enzymatic reaction between glucose oxidase and glucose. Poly(MPC) (PMPC) was easily degraded in H(2)O(2) aqueous solution, and the PMPC hydrogel was also degraded in H(2)O(2) aqueous solution. The degradation mechanism was considered to be main chain scission of PMPC. The degradation profile was evaluated by using weight swelling ratio and volume swelling ratio. The weight swelling ratio of PMPC hydrogel firstly increased due to the reduction of crosslink density, then the ratio decreased to zero (complete degradation). The degradation profile was proportional to the H(2)O(2) concentration. Furthermore, volume swelling ratio also increased, and complex elastic modulus decreased with degradation in H(2)O(2) aqueous solution. These results indicated that the hydrogel was degraded by hydroxy and/or hydroperoxy radicals which was produced by H(2)O(2), the crosslink density and mechanical property decreased. The release profile from the hydrogel was estimated by using lipid microsphere (LM) as an insulin model. The LM was released with the degradation of PMPC hydrogel. Taking these results into account, the PMPC hydrogel was available for H(2)O(2) degradable hydrogel for synchronization with glucose concentration by using enzymatic reaction.
本研究的目的是确定H₂O₂可降解水凝胶用于制备与培养基中葡萄糖浓度变化同步的胰岛素释放系统的适用性。该水凝胶通过使用2-甲基丙烯酰氧基乙基磷酰胆碱（MPC）和交联剂制备。水凝胶的有利特性是对H₂O₂浓度有响应性降解。H₂O₂是通过葡萄糖氧化酶和葡萄糖之间的酶促反应产生和利用的。聚（MPC）（PMPC）在H₂O₂水溶液中容易降解，PMPC水凝胶在H₂O₂水溶液中也会降解。降解机制被认为是PMPC的主链断裂。通过使用重量溶胀率和体积溶胀率来评估降解情况。PMPC水凝胶的重量溶胀率首先由于交联密度的降低而增加，然后该比率降至零（完全降解）。降解情况与H₂O₂浓度成正比。此外，在H₂O₂水溶液中降解时，体积溶胀率也增加，复合弹性模量降低。这些结果表明，水凝胶被H₂O₂产生的羟基和/或氢过氧自由基降解，交联密度和机械性能降低。通过使用脂质微球（LM）作为胰岛素模型来估计水凝胶的释放情况。LM随着PMPC水凝胶的降解而释放。考虑到这些结果，PMPC水凝胶可用于通过酶促反应与葡萄糖浓度同步的H₂O₂可降解水凝胶。
