Evaluation of crosslinked chitosan hydrogels as carriers for prolonged delivery of some novel nitric oxide donor compounds based on theophylline and paracetamol

Abstract

The hydrogels of crosslinked chitosan with different glutaraldehyde amounts have been "in vitro" tested as carriers for prolonged release of some drugs for inflammatory and bronchopulomonary diseases. These hydrogels have been loaded with two novel nitric oxide donors, derivatives of 7-[2-nitroxyacethyl-oxy-3-(4-acethyl-amino-phenoxy)-propyl]-8-R-1, 3-dimethyl-xanthine compounds (R=H, NO2 for 65 and respectively 77 compounds) designed as multitarget drugs and parent compounds as paracetamol, theophylline, two xanthine derivatives 7-[2-hydroxy-3-(4-acethyl-amino-phenoxy)- propyl]-8-R-1,3-dimethyl-xanthine derivatives with (R=H, NO2 for D1 and respectively D2) and their release was evaluated in an acidic solution (pH=2.2) simulating the gastric fluid. Results have been correlated with the swelling behaviour which was also followed in acidic media with pH=2.2. The relationships between the release profiles and kinetics and matrix characteristics and/or drug properties have been established.