Synthesis and physicochemical analysis of gelatin-based hydrogels for drug carrier matrices

Abstract

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 (Tmax) and the time to failure by hydrolysis (Tfail), but had little effect on the maximum swelling weight ratio (Rmax) and the weight ratio at failure (Rfail). Modification of gelatin with EDTAD generally had no effect on Tmax and Tfail, but increased Rmax and Rfail. Modification of gelatin with PEG-dial and EDTAD increased Rmax, but had no effect on Tmax, Rfail, or Tfail. Decreasing percent glutaraldehyde fixation generally increased Rmax and Rfail but decreased Tmax and Tfail. 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 (Dmax) and the time to reach Dmax (Tdmax). Percent glutaraldehyde fixation did not significantly affect Dmax or Tdmax (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 21d. © 2002 Elsevier Science Ltd. All rights reserved.