Polymeric Chitosan Gel Modulates Inflammatory Responses to Prevent Peritoneal Adhesion in Rats
Abstract
Peritoneal adhesions are a pathological response to injury that connects adjacent structures that cause by inflammatory response such as IL-1 and IL-6. The current strategies to minimize or prevent peritoneal adhesions are very limited. Chitosan was found have antiinflammatory effect. However, chitosan hydropphobic properties give poor solubility in physiological solvent such as peritoneal fluid. Our study aims to investigate the effect of polymeric chitosan gel in the prevention of peritoneal adhesion through modulating IL-1 and IL-6 after laparotomy.
Ten rats were divided into a control group and treated group. Laparotomy model was done with proper procedure. Illeum were scratch using cytobrush to mimic peritoneal adhesions. In the treated group, the defect was covered with Mediclore®. After 14 days, IL-1 and IL-6 were analyzed using ELISA from peritoneal fluid serum and macroscopic observation of adhesion were made.
All animals in control group showed high grade of adhesin while treated group showed a filmy peritoneal adhesion. Group treated with Mediclore® showed a lower IL-1 levels compared to control group. Treated group showed a better control at inflammation by scoring lower IL-6 levels compared to control group.
In conclusion, polymeric chitosan gel prevents peritoneal adhesions through modulation of inflammatory cytokines after laparotomy in rats.
Keywords: chitosan, IL-1, IL-6, peritoneal adhesions, laparotomy
References
2. Akbaba S, Atila D, Keskin D, Tezcaner T, Tezcaner A. Multilayer fibroin/chitosan oligosaccharide lactate and pullulan immunomodulatory patch for treatment of hernia and prevention of intraperitoneal adhesion. Carbohydrate Polymers. 2021;265:118066. doi:10.1016/j.carbpol.2021.118066
3. Amano Y, Qi P, Nakagawa Y, Kirita K, Ohta S, Ito T. Prevention of Peritoneal Adhesions by Ferric Ion-Cross-Linked Hydrogels of Hyaluronic Acid Modified with Iminodiacetic Acids. ACS Biomater Sci Eng. 2018;4(9):3405-3412. doi:10.1021/acsbiomaterials.8b00456
4. Hyun H, Hashimoto-Hill S, Kim M, Tsifansky MD, Kim CH, Yeo Y. Succinylated Chitosan Derivative Has Local Protective Effects on Intestinal Inflammation. ACS Biomater Sci Eng. 2017;3(8):1853-1860. doi:10.1021/acsbiomaterials.7b00262
5. Pourgholaminejad A, Aghdami N, Baharvand H, Moazzeni SM. The effect of pro-inflammatory cytokines on immunophenotype, differentiation capacity and immunomodulatory functions of human mesenchymal stem cells. Cytokine. 2016;85:51-60. doi:10.1016/j.cyto.2016.06.003
6. Morris JL, Cross SJ, Lu Y, et al. Live imaging of collagen deposition during skin development and repair in a collagen I – GFP fusion transgenic zebrafish line. Developmental Biology. Published online June 2018. doi:10.1016/j.ydbio.2018.06.001
7. Shamekhi F, Tamjid E, Khajeh K. Development of chitosan coated calcium-alginate nanocapsules for oral delivery of liraglutide to diabetic patients. International Journal of Biological Macromolecules. 2018;120:460-467. doi:10.1016/j.ijbiomac.2018.08.078
8. Mitsuhashi K, Qi P, Takahashi A, Ohta S, Ito T. Prevention of postoperative peritoneal adhesions in rats with sidewall defect-bowel abrasions using metal ion-crosslinked N-succinyl chitosan hydrogels. Reactive and Functional Polymers. 2019;145:104374. doi:10.1016/j.reactfunctpolym.2019.104374
9. Naito M, Ogura N, Yamanashi T, et al. Prospective randomized controlled study on the validity and safety of an absorbable adhesion barrier (Interceed®) made of oxidized regenerated cellulose for laparoscopic colorectal surgery: Adhesion barrier for colorectal surgery. Asian J Endosc Surg. 2017;10(1):7-11. doi:10.1111/ases.12334
10. Cheng F, Wu Y, Li H, et al. Biodegradable N, O-carboxymethyl chitosan/oxidized regenerated cellulose composite gauze as a barrier for preventing postoperative adhesion. Carbohydrate Polymers. 2019;207:180-190. doi:10.1016/j.carbpol.2018.10.077
11. Lauder CIW, Garcea G, Strickland A, Maddern GJ. Use of a Modified Chitosan–Dextran Gel to Prevent Peritoneal Adhesions in a Rat Model. Journal of Surgical Research. 2011;171(2):877-882. doi:10.1016/j.jss.2010.06.028
12. Yan S, Wang T, Li X, et al. Fabrication of injectable hydrogels based on poly( L -glutamic acid) and chitosan. RSC Adv. 2017;7(28):17005-17019. doi:10.1039/C7RA01864A
13. Sakoda M, Kaneko M, Ohta S, et al. Injectable Hemostat Composed of a Polyphosphate-Conjugated Hyaluronan Hydrogel. Biomacromolecules. 2018;19(8):3280-3290. doi:10.1021/acs.biomac.8b00588
14. Zhang S, Xu Z, Wen X, Wei C. A nano chitosan membrane barrier prepared via Nanospider technology with non-toxic solvent for peritoneal adhesions’ prevention. J Biomater Appl. 2021;36(2):321-331. doi:10.1177/08853282211008109
15. Duan H, Lü S, Qin H, et al. Co-delivery of zinc and 5-aminosalicylic acid from alginate/N-succinyl-chitosan blend microspheres for synergistic therapy of colitis. International Journal of Pharmaceutics. 2017;516(1-2):214-224. doi:10.1016/j.ijpharm.2016.11.036
16. Nakagawa Y, Ohta S, Sugahara A, Okubo M, Yamada A, Ito T. In Vivo Redox-Responsive Sol–Gel/Gel–Sol Transition of Star Block Copolymer Solution Based on Ionic Cross-Linking. Macromolecules. 2017;50(14):5539-5548. doi:10.1021/acs.macromol.7b01020
17. Xu L, Huang YA, Zhu QJ, Ye C. Chitosan in Molecularly-Imprinted Polymers: Current and Future Prospects. IJMS. 2015;16(8):18328-18347. doi:10.3390/ijms160818328
18. Pan M, Tang Z, Tu J, et al. Porous chitosan microspheres containing zinc ion for enhanced thrombosis and hemostasis. Materials Science and Engineering: C. 2018;85:27-36. doi:10.1016/j.msec.2017.12.015
19. Poosapati A, Negrete K, Thorpe M, et al. Safe and flexible chitosan‐based polymer gel as an electrolyte for use in zinc‐alkaline based chemistries. J Appl Polym Sci. 2021;138(33):50813. doi:10.1002/app.50813
20. Wang W, Meng Q, Li Q, et al. Chitosan Derivatives and Their Application in Biomedicine. IJMS. 2020;21(2):487. doi:10.3390/ijms21020487