Modulating Functional Pendant Groups of Poly(ethylene glycol) Hydrogels for Refined Control of Drug Release

Abstract

Hydrogels are highly attractive delivery vehicles for therapeutic proteins. Their innate biocompatibility, hydrophilicity and aqueous permeability allow stable encapsulation and release of proteins. The release rates also can be controlled simply by altering the crosslinking density of the polymeric network. However, the crosslinking density also influences the mechanical properties of hydrogels, generally opposite to the permeability. In addition, the release of larger proteins may be hindered below critically diminished porosity determined by the crosslinking density. Herein, the physical properties of the hydrogels are tuned independent of crosslinking density by presenting functional pendant chains. Heterobifunctional poly(ethylene glycol) monoacrylate (PEGMA) with various end functional groups is synthesized and copolymerized with PEG diacrylate (PEGDA) to engineer PEG hydrogels with pendant PEG chains. The release rates of proteins with different isoelectric points could be effectively controlled by the type and the density of functional pendant chains of the PEG hydrogels; sulfonate (negative charge), trimethylammonium chloride (positive charge), and phenyl (hydrophobic). The therapeutic potential of this hydrogel system was also validated with in vitro studies, further demonstrating its potential as refined protein delivery.