Controlled release of biomolecules from temperature-sensitive hydrogels prepared by radiation polymerization

Poly(acryloyl-L-proline methyl ester)-based hydrogels containing 1 and 5% o f a crosslinking agent were studied as drug delivery systems. The drug load ing properties were investigated by matrix incubation into solutions contai ning biomolecules with molecular weight ranging between 300 and 65 000 Da. The loading yield was found to depend on both the crosslinking degree and t he molecular weight of the drug. In vitro release studies were carried out with both swollen and dry matrices loaded with gentamicin, isoniazid and in sulin. Gentamicin and isoniazid were released by a bimodal Fickian diffusio n with a remarkable burst that was found to depend on both matrix crosslink ing degree and physical state. In vivo, the subcutaneous implantation into mice of the isoniazid loaded matrices allowed for an efficient drug release for 800 h. In vitro insulin was released from the swollen matrices for 150 0 h by diffusional Fickian mechanism while the dry ones displayed a lag tim e followed by Fickian diffusion release. The subcutaneous implantation of t he insulin-loaded matrices into diabetic mice induced a remarkable decrease in the glucose concentrations in blood. In particular, the dry 1% matrices were found to maintain a low glucose level for 700 h. (C) 2001 Elsevier Sc ience BY. All rights reserved.