Jing Zi-Wei, Ma Zhi-Wei, Li Chen, Jia Yi-Yang, Luo Min, Ma Xi-Xi, Zhou Si-Yuan, Zhang Bang-Le
Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, PR China.
Qindu Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
Bioorg Med Chem Lett. 2017 Feb 15;27(4):1003-1006. doi: 10.1016/j.bmcl.2016.12.072. Epub 2016 Dec 31.
The covalently cross-linked chitosan-poly(ethylene glycol) derivatives have been developed as a controlled release system with potential for the delivery of protein drug. The swelling characteristics of the hydrogels based on these derivatives as the function of different PEG content and the release profiles of a model protein (bovine serum albumin, BSA) from the hydrogels were evaluated in simulated gastric fluid with or without enzyme in order to simulate the gastrointestinal tract conditions. The derivatives cross-linked with difunctional PEG-dialdehyde via reductive amination can swell in alkaline pH and remain insoluble in acidic medium. The cumulative release amount of BSA was relatively low in the initial 2h and increased significantly at pH 7.4 with intestinal lysozyme for additional 12h. The results proved that the release-and-hold behavior of the cross-linked CS-PEGH-CS hydrogel provided a swell and intestinal enzyme controlled release carrier system, which is suitable for oral protein drug delivery.
共价交联的壳聚糖 - 聚（乙二醇）衍生物已被开发为一种控释系统，具有递送蛋白质药物的潜力。基于这些衍生物的水凝胶在不同聚乙二醇含量下的溶胀特性以及模型蛋白（牛血清白蛋白，BSA）从水凝胶中的释放曲线，在有或没有酶的模拟胃液中进行了评估，以模拟胃肠道条件。通过还原胺化与双功能聚乙二醇二醛交联的衍生物在碱性pH值下会溶胀，在酸性介质中保持不溶。在最初的2小时内，BSA的累积释放量相对较低，在pH 7.4且有肠道溶菌酶的情况下，在接下来的12小时内显著增加。结果证明，交联的CS - PEGH - CS水凝胶的释放 - 保持行为提供了一种溶胀和肠道酶控释载体系统，适用于口服蛋白质药物递送。
