Enzymatically degradable nitric oxide releasing S-nitrosated dextran thiomers for biomedical applications

Abstract

Herein we report the development and evaluation of enzymatically degradable nitric oxide (NO) releasing S-nitrosated dextran thiomers as potent biomedical materials. These materials are characterized by their specificity to release NO under arterial blood conditions, followed by their susceptibility to undergo enzymatic degradation by dextranase. The very specific conjugation chemistries we employed for the thiol incorporation resulted in characteristic stabilization of the resulting S-nitrosothiol moieties, and consequently yielded stable pro-drugs for the storage and controlled delivery of NO. We evaluated the extent of NO loading and release kinetics using multiple and independent analytical techniques, and related these to the structure and environment associated with the thiol moiety incorporated onto the dextran backbone. Finally, the enzymatic degradation kinetics was followed by monitoring the molecular weight profile using gel permeation chromatography, and the results were interpreted using well-established model predictions.