Synthesis of poly(glutamic acid)-tyramine hydrogel by enzyme-mediated gelation for controlled release of proteins.

An in situ-formed hydrogel was synthesized by enzymatic cross-linking of poly(γ-glutamic acid)–tyramine conjugates (PGA–Tyr) using horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). The gelation time ranged from 25 s to 5 min was accomplished by tuning the concentration of HRP, H2O2/Tyr molar ratio and the degree of substitution (DS) of Tyr groups. The storage modulus (G′), cross-link density, and mesh size can be tailored by controlling the H2O2/Tyr ratio and DS. The rheological analysis indicated that the storage modulus (G′) can be tailored from approximately 40 to over 1100 Pa with the increasing H2O2/Tyr ratio and DS. The bovine serum albumin (BSA) was used as model protein and encapsulated into the hydrogel during the enzyme-mediated cross-linking reaction. Controlled release of BSA in vitrofrom the PGA–Tyr hydrogel was obtained. The release rate and cumulative release amount of encapsulated BSA were manipulated by controlling the H2O2/Tyr ratio and DS. More than 90% of encapsulated BSA was released from the hydrogel with low cross-link density and lager mesh size in 60 h, while only 68% of BSA was released from the hydrogel with high cross-link density and small mesh size. The results indicated that the PGA–Tyr hydrogel is a promising material for the controlled release of therapeutic protein or peptides. [ABSTRACT FROM AUTHOR]