Controlled release of Mitomycin C from modified cellulose based thermo-gel prevents post-operative de novo peritoneal adhesion.

The complications from surgery associated peritoneal adhesion can be alleviated by combination of physical isolation and pharmaceutical treatment. This work aims to develop thermo-sensitive hydrogel barrier by combining mitomycin C (MMC) with modified tempo oxidized nanocellulose (cTOCN) through EDC/NHS-chemical conjugation followed by integration with methyl cellulose (MC). The MMC was successfully combined with cTOCN and ensured controlled release of MMC from hydrogel throughout 14 days. Amount of MC (1.5, 2.5, 3.5% w/v) was proportional to gelation time and inversely proportional to degradation of hydrogel. The optimized hydrogel (C2.5T1M0.2) needed only 30 s for thermoreversible sol-gel (4℃-37℃) phenomenon and did not show in vitro fibroblast cells toxicity as well as ensured complete adhesion prevention efficacy, reperitonealization in rat side wall-cecal abrasion model. Overall, the developed C2.5T1M0.2 thermo-gel advances state-of-the-art in view of cytocompatibility, mechanical stability, optimum degradation, good injectability, sustain drug release from surgical sites, and satisfactory de novo anti-adhesion capacity.

TEMPO oxidized nano-cellulose containing thermo-responsive injectable hydrogel for post-surgical peritoneal tissue adhesion prevention.

The objective of this study was to present an effective injectable adhesion barrier comprised of TEMPO-oxidized cellulose nanofiber (TOCN), methyl cellulose, carboxymethyl cellulose, and polyethylene glycol. Hydrogels with different concentrations (0.2, 0.5, 0.8, 1% w/v) of bio compatible TOCN were investigated to determine their abilities to prevent post-surgical peritoneal adhesion using a rat cecal wall abrasion model. Sol-gel transition at body temperature (37 °C) was optimized by adjusting concentration of sodium ions (Na+), with a gelation time of 45 ±â€¯7 s. These TOCN containing hydrogels showed non cytotoxicity to rat bone marrow mesenchymal stem cells (RBMSCs) and L929 fibroblast cells as cell models during in vitro assessment. Degradation studies revealed that, TOCN concentration in hydrogel was inversely proportional to hydrolytic degradation rate. From in vivo evaluations, TOCN 0.2 hydrogel significantly reduced peritoneal adhesion in rat (n = 8) compared to untreated controls based on gross observation, histological analysis, and expression analysis of marker proteins. By taking advantages of thermo gelling, high stability, non-invasive way of application and rapid recovery potential, TOCN containing bio compatible hydrogel could be used as a cost-effective barrier to efficiently inhibit post-surgical peritoneal adhesions.