Einerson Nicole J, Stevens Kelly R, Kao Weiyuan John
Department of Biomedical Engineering, College of Engineering, University of Wisconsin-Madison, Madison, WI 53705, USA.
Biomaterials. 2003 Feb;24(3):509-23. doi: 10.1016/s0142-9612(02)00369-1.
This study examined the interrelated effect of environmental pH, gelatin backbone modification and crosslinking modality on hydrogel morphology, surface hydrophilicity, in vitro swelling/degradation kinetics, in vitro drug release kinetics and in vivo degradation, inflammatory response and drug release activity. The percent glutaraldehyde fixation had a greater impact on the morphology of the dehydrated hydrogels than gelatin modification. Any decrease in percent glutaraldehyde fixation and/or modification of gelatin with polyethylene glycol dialdehyde (PEG-dial) and/or ethylenediaminetetraacetic dianhydride (EDTAD) increased hydrogel surface hydrophilicity. Swelling/degradation studies showed that modification of gelatin with PEG-dial generally increased the time to reach the maximum swelling weight ratio (T(max)) and the time to failure by hydrolysis (T(fail)), but had little effect on the maximum swelling weight ratio (R(max)) and the weight ratio at failure (R(fail)). Modification of gelatin with EDTAD generally had no effect on T(max) and T(fail), but increased R(max) and R(fail). Modification of gelatin with PEG-dial and EDTAD increased R(max), but had no effect on T(max), R(fail), or T(fail). Decreasing percent glutaraldehyde fixation generally increased R(max) and R(fail) but decreased T(max) and T(fail). Decreasing environmental pH from 7.4 to 4.5 had no effect on any swelling/degradation properties. In vitro drug release studies showed that modification of gelatin with PEG-dial and/or EDTAD generally decreased the maximum mass ratio of drug released (D(max)) and the time to reach D(max) (T(dmax)). Percent glutaraldehyde fixation did not significantly affect D(max) or T(dmax) (except for EDTAD-modified gelatin hydrogels). In vivo studies showed that gelatin-based hydrogels elicited comparable levels of acute and chronic inflammatory response as that of the empty cage control by 21 d.
本研究考察了环境pH值、明胶主链修饰和交联方式对水凝胶形态、表面亲水性、体外溶胀/降解动力学、体外药物释放动力学以及体内降解、炎症反应和药物释放活性的相互关联影响。戊二醛固定百分比对脱水水凝胶形态的影响大于明胶修饰。戊二醛固定百分比的任何降低和/或用聚乙二醇二醛（PEG-dial）和/或乙二胺四乙酸二酐（EDTAD）对明胶进行修饰都会增加水凝胶表面亲水性。溶胀/降解研究表明，用PEG-dial修饰明胶通常会增加达到最大溶胀重量比的时间（T(max)）和水解失效时间（T(fail)），但对最大溶胀重量比（R(max)）和失效时的重量比（R(fail)）影响较小。用EDTAD修饰明胶通常对T(max)和T(fail)没有影响，但会增加R(max)和R(fail)。用PEG-dial和EDTAD修饰明胶会增加R(max)，但对T(max)、R(fail)或T(fail)没有影响。降低戊二醛固定百分比通常会增加R(max)和R(fail)，但会降低T(max)和T(fail)。将环境pH值从7.4降至4.5对任何溶胀/降解特性均无影响。体外药物释放研究表明，用PEG-dial和/或EDTAD修饰明胶通常会降低药物释放的最大质量比（D(max)）和达到D(max)的时间（T(dmax)）。戊二醛固定百分比对D(max)或T(dmax)没有显著影响（EDTAD修饰明胶水凝胶除外）。体内研究表明，基于明胶的水凝胶在21天时引发的急性和慢性炎症反应水平与空笼对照组相当。
