Glucose-Initiated Accelerated Degradation of Poly (Beta-amino Ester) Hydrogels for Drug Delivery

Hydrogels have long been used in the development of a range of applications such as intelligent drug delivery systems, tissue engineering, orthopedic implants, and other medical applications.  Their three-dimensional structure, formed by crosslinking chains, allows them to absorb large quantities of water, thereby mimicking many soft tissues. Currently, there is a significant interest in intelligent drug delivery systems for the treatment of diabetes, and hydrogels could offer a unique platform for such applications provided they could sense and respond to glucose.  For drug delivery, a hydrogel can be loaded with, and subsequently release, a drug in response to environmental stimuli.  For degradable hydrogels, this response is the hydrolytic or enzymatic cleavage of chemical bonds resulting in erosion of the three-dimensional network.  For biomedical applications, poly (ethylene glycol) (PEG) is one of the most widely used polymers in hydrogels. Additionally, common PEG precursors can be combined with amines to form poly (b-amino ester) (PBAEs) hydrogels that are hydrolytically degradable as opposed to traditionally non-degradable PEG-based hydrogels.  This project aims to investigate the rate of glucose-initiated degradation of hydrogels by measuring the mass loss ratio of the gels at different points of time.  Macromers used for PBAE hydrogels were synthesized with a diacrylate:primary amine ratio of 1.2:1 using isobutylamine and varying ratios of PEG 400 diacrylate (PEG400DA) and diethylene glycol diacrylate (DEGDA).  PBAE hydrogels with were synthesized by UV polymerization with 2,2 – dimethoxy-2-phenylacetophenone as a photoinitiator and DMSO as the solvent.  The molar ratios of DEGDA:PEG400DA were varied at 1:1, 3:1 and 10:1 with the latter being the most hydrophobic and therefore displaying the longest degradation profile.  Studies show that glucose and glucose oxidase reaction products are able to accelerate the degradation of PBAE hydrogels. The ability to accelerate the degradation of hydrogels by sensing glucose provides a platform for intelligent drug delivery systems composed of biocompatible materials with great potential for biomedical applications.