A chitosan/dextran-based (CD) hydrogel has been developed as a post-surgical aid for endoscopic sinus surgery, and has been successful in preventing adhesion formation in human and animal trials. Interest in extending the use of this hydrogel for abdominal and spinal surgeries has prompted the necessity to reduce cytotoxicity observed in vitro.
The CD hydrogel is formed by cross-linking between aldehyde groups present in dextran aldehyde (DA) and the amine groups on the succinylated chitosan. The active component, dextran aldehyde, was formulated to a lower degree of oxidation (from 80% to 25%) to reduce cytotoxicity. The antimicrobial activity of the lower oxidized hydrogel component was investigated against 6 common species found in post-operative abdominal infections. This was examined by the micro-broth dilution test and time course growth experiments. The reduction in oxidation of DA resulted in a decrease in antimicrobial efficacy in both the DA alone and CD hydrogel. However, the 25% oxidized dextran was still viable candidate to use for abdominal surgery, as both formulations of dextran aldehyde were more effective against anaerobes than aerobic species.
In order to determine the number of free aldehyde groups present, investigations into the chemical nature of the hydrogel over time were performed by gel 1H-NMR spectroscopy. Gel 1H NMR indicated a clear decrease in both the amine and aldehyde peaks as the gel components created cross-links; thereby, reducing the number of free aldehydes available for antimicrobial activity. Our studies surmise that reducing the level of oxidation, i.e. the number of free aldehydes in dextran aldehyde, results in a reduction in antimicrobial efficacy but that anti-anaerobe activity is still retained.