Hydrolytic and enzymatic degradation of poly(gamma-glutamic acid) hydrogels and their application in slow-release systems for proteins

The hydrolytic and enzymatic degradation of newly developed hydrogels, produced by crosslinking purified poly(gamma-glutamic acid) (gamma PGA) with dihaloalkane compounds, was studied and is reported in this paper. Analysis of hydrolysis of the hydrogel as a function of pH indicated that the hydrolysis occurred slowly at neutral pH, but fast in both acidic and alkaline solutions, while the polymer could be hydrolyzed rapidly only in acidic solutions. The ester bonds were more sensitive to hydrolysis than peptide bonds. The biodegradability of the hydrogel and polymer was further confirmed when enzymatic degradation was studied by three enzymes (cathepsin B, pronase E, and trypsin), which were able to cleave both ester and peptide bonds gradually. A slow-release system for porcine somatotropin (pST) formed by using the hydrogel as matrix to entrap the hormone was evaluated in vitro and in vivo. Results demonstrated that the hydrogel was able to release the hormone for a period of 20-30 days and indicated its potential application in slow-release systems for bioactive materials, especially macromolecules, such as peptides and proteins.