Protein delivery from materials formed by self-selective conjugate addition reactions

A new chem. crosslinking scheme was utilized for the formation of degradable poly(ethylene glycol) hydrogels suitable for the delivery of protein drugs. An aq. soln. contg. a PEG-multiacrylate and solid particles of albumin was mixed with an aq. soln. contg. a PEG-dithiol, rapidly producing a cross-linked hydrogel through a Michael-type addn. reaction. For some formulations, it was obsd. that about 65% of the incorporated protein was released with zero-order kinetics over a period of about 4 days. By changing the functionality of the cross-linker, the release of protein could even be delayed for about 4 days, followed by zero-order release. The mechanism for release appeared to be a combination of slow dissoln. of protein in the presence of PEG and hindered diffusion of protein through the gel. The crosslinking of the gels was studied rheometrically, and the hydrolytic degrdn. of the gels was characterized by measuring the swelling of the gels. Biochem. anal. of the released proteins demonstrated that the polymers reacted with each other, but not with proteins. Utilizing the Flory-Rehner and Peppas-Merrill equations, a framework for modeling the protein release from the gels is described. [on SciFinder (R)]