Protein delivery from materials formed by self-selective conjugate addition reactions
Protein delivery from materials formed by self-selective conjugate addition reactions
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DOI：
10.1016/s0168-3659(01)00398-4
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发表时间：
2001-09-11
影响因子：
10.8
通讯作者：
Hubbell, JA
中科院分区：
文献类型：
--
作者：
Elbert, DL;Pratt, AB;Hubbell, JA
一种新的化学交联方案用于形成可降解的聚乙二醇水凝胶，适用于蛋白质药物的递送。将含有聚乙二醇-多丙烯酸酯和白蛋白固体颗粒的水溶液与含有聚乙二醇-二硫醇的水溶液混合，通过迈克尔型加成反应快速生成交联水凝胶。对于某些配方，观察到约65%的掺入蛋白质在大约4天的时间内以零级动力学释放。通过改变交联剂的功能，蛋白质的释放甚至可以延迟约4天，然后是零级释放。释放的机制似乎是蛋白质在PEG存在下缓慢溶解和蛋白质通过凝胶扩散受阻的结合。用流变学方法研究了交联凝胶的交联反应，并通过测定凝胶的溶胀来表征凝胶的水解降解。对释放出的蛋白质进行生化分析表明，这些聚合物可以相互反应，但不能与蛋白质反应。利用Flory-Rehner和Peppas-Merrill方程，描述了从凝胶中模拟蛋白质释放的框架。(C) 2001 Elsevier Science B.V.版权所有
A new chemical cross-linking scheme was utilized for the formation of degradable poly(ethylene glycol) hydrogels suitable for the delivery of protein drugs. An aqueous solution containing a PEG-multiacrylate and solid particles of albumin was mixed with an aqueous solution containing a PEG-dithiol, rapidly producing a cross-linked hydrogel through a Michael-type addition reaction. For some formulations, it was observed that about 65% of the incorporated protein was released with zero-order kinetics over a period of about 4 days. By changing the functionality of the cross-linker, the release of protein could even be delayed for about 4 days, followed by zero-order release. The mechanism for release appeared to be a combination of slow dissolution of protein in the presence of PEG and hindered diffusion of protein through the gel. The cross-linking of the gels was studied rheometrically, and the hydrolytic degradation of the gels was characterized by measuring the swelling of the gels. Biochemical analysis of the released proteins demonstrated that the polymers reacted with each other, but not with proteins. Utilizing the Flory-Rehner and Peppas-Merrill equations, a framework for modeling the protein release from the gels is described. (C) 2001 Elsevier Science B.V. All rights reserved.