Elbert D L, Pratt A B, Lutolf M P, Halstenberg S, Hubbell J A
Institute for Biomedical Engineering and Department of Materials, Swiss Federal Institute of Technology and University of Zurich, Moussonstrasse 18, CH-8044, Zurich, Switzerland.
J Control Release. 2001 Sep 11;76(1-2):11-25. doi: 10.1016/s0168-3659(01)00398-4.
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.
一种新的化学交联方案被用于形成适用于蛋白质药物递送的可降解聚乙二醇水凝胶。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迅速产生交联水凝胶。对于某些配方，观察到约65%的包封蛋白质在约4天的时间内以零级动力学释放。通过改变交联剂的官能度，蛋白质的释放甚至可以延迟约4天，随后是零级释放。释放机制似乎是蛋白质在聚乙二醇存在下的缓慢溶解以及蛋白质通过凝胶的扩散受阻的组合。通过流变学研究了凝胶的交联，并通过测量凝胶的溶胀来表征凝胶的水解降解。对释放蛋白质的生化分析表明，聚合物相互反应，但不与蛋白质反应。利用弗洛里-雷纳方程和佩帕斯-梅里尔方程，描述了一个模拟蛋白质从凝胶中释放的框架。
