n-succinyl-chitosan and Disease-Models--Animal

The present study developed novel zinc ion cross-linked alginate/N-succinyl-chitosan (NSC) blend microspheres (MS) for co-delivery of zinc and 5-aminosalicylic acid (5-ASA) for synergistic therapy of colitis. Physicochemical characterization of blend MS was assessed using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and energy dispersive X-ray spectrometer (EDS). In vitro release studies demonstrated that blend MS has a pH-dependent release property. Both 5-ASA and zinc have lower release in acid medium and higher release in colonic environment. The therapeutic efficacy of zinc cross-linked blend MS was evaluated using induced-colitis rat models, and showed a superior treatment effect in alleviating inflammation of colitis rats. No systemic toxicity was observed after oral administration of blend MS. Therefore, zinc ion cross-linked alginate/N-succinyl-chitosan blend MS appeared to be a good candidate for co-delivery of zinc and 5-ASA to colon, and had great potential application in inflammatory bowel diseases (IBD) treatment.

Topics: Administration, Oral; Alginates; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chitosan; Colitis; Disease Models, Animal; Drug Carriers; Drug Combinations; Drug Delivery Systems; Drug Liberation; Drug Synergism; Glucuronic Acid; Hexuronic Acids; Hydrogen-Ion Concentration; Male; Mesalamine; Microscopy, Electron, Scanning; Microspheres; Rats; Rats, Wistar; Spectroscopy, Fourier Transform Infrared; Zinc

How to shorten the immune convalescence required after transplantation in recipients is still an austere medicinal problem. Speed-up recovery means less infection opportunity and high survival. In this study, an immune-deficient mouse model was developed by lethally irradiation to evaluate the immune reconstitution effect of N-Succinyl-Chitosan (NSC), a water soluble low molecular weight chitosan derivative, after umbilical cord blood stem cells transplantation, including hematopoiesis parameters detection, T-cell phenotype analysis and pathological comparison; effects of NSC on proliferation of umbilical cord blood stem cell has also been evaluated in vitro. By comparison and analysis, we found the combination of NSC and hematopoietic growth factors could dramatically shorten the time required for the recovery of hematopoiesis, T-cell phenotype and injured spleen after transplantation, suggesting that NSC may hasten the immune recovery and therefore may shorten the time of exposure to life-threatening opportunistic infections in transplant recipients. Moreover, we demonstrated that NSC was effective on the proliferation and clone of umbilical cord stem cell in vitro, suggesting NSC could speed up the immune reconstitution in umbilical cord blood transplantation by enlarge the number of umbilical cord blood stem cell.

Topics: Animals; Cell Proliferation; Chitosan; Cord Blood Stem Cell Transplantation; Disease Models, Animal; Hematopoiesis; Hematopoietic Cell Growth Factors; Humans; Immune System; Male; Mice; Opportunistic Infections; Spleen; T-Lymphocytes; Time Factors

5-Aminosalicylic acid (5-ASA) loaded N-Succinyl-chitosan (SucCH) microparticle and freeze-dried system were prepared as potential delivery systems to the colon. Physicochemical characterization and in vitro release and swelling studies were previously assessed and showed that the two formulations appeared to be good candidates to deliver the drug to the colon. In this work the effectiveness of these two systems in the treatment of inflammatory bowel disease was evaluated. In vitro mucoadhesive studies showed excellent mucoadhesive properties of both the systems to the inflamed colonic mucosa. Experimental colitis was induced by rectal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into male Wistar rats. Colon/body weight ratio, clinical activity score system, myeloperoxidase activity and histological evaluation were determined as inflammatory indices. The two formulations were compared with drug suspension and SucCH suspension. The results showed that the loading of 5-ASA into SucCH polymer markedly improved efficacy in the healing of induced colitis in rats.

Topics: Absorption; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chitosan; Colitis; Colon; Disease Models, Animal; Drug Carriers; Drug Delivery Systems; Freeze Drying; Intestinal Mucosa; Lymphocyte Activation; Male; Mesalamine; Organ Size; Peroxidase; Polymers; Rats; Rats, Wistar; Trinitrobenzenesulfonic Acid