Eudragit S100 coated iron oxide-chitosan nanocomposites for colon targeting of 5-aminosalicylic acid ameliorate ulcerative colitis by improving intestinal barrier function and inhibiting NLRP3 inflammasome

The therapeutic effect of 5-amino salicylic acid (5-ASA), a first-line therapeutic agent for the treatment of ulcerative colitis (UC), is limited by the modest bioavailability afforded by its oral administration. In this study, a 5-ASA oral delivery system was developed using Eudragit S100-coated iron oxide-chitosan nanocomposites (ES-IOCS/5-ASA) to address this issue. According to drug release studies in vitro, ES-IOCS/5-ASA only released a small amount of drug in simulated gastric fluid with a pH of 1.2.

Highlights

In this study, pH-triggered delivery of 5-ASA using Eudragit S100 coated iron oxide-chitosan nanocomposites (ES-IOCS/5-ASA) was developed.

In vitro studies report that 5-ASA loaded iron oxide-chitosan nanocomposites (IOCS/5-ASA) achieved significant cellular uptake and evident anti-inflammatory activity. In vivo, the oral administration of ES-IOCS/5-ASA ameliorated DSS-induced colitis, and the underlying mechanisms might involve revising the integrity of the intestinal barrier.

For ES-IOCS/5-ASA, Eudragit S100 created a thick layer on the nanocomposites surface, which could prevent the early release of 5-ASA in an acidic environment.

Iron oxide nanoparticles may decrease the degree of oxidative stress in cells and serve as anti-inflammatory and antioxidant agents.

This study provides a promising approach for the effective treatment of ulcerative colitis, which serves as a reliable drug delivery system targeted specifically for the colon.

However, in a medium with a pH of 7.5, a relatively rapid and complete release was noted. 5-ASA-loaded iron oxide-chitosan nanocomposites (IOCS/5-ASA) could be effectively taken up by NCM460 cells and performed better anti-inflammatory effects than free 5-ASA. At the same time, IOCS/5-ASA improved barrier damage in DSS-induced NCM460 cells. In vivo models of dextran sulphate sodium (DSS)-induced colitis were used to assess the therapeutic efficacy of oral administration of ES-IOCS/5-ASA. ES-IOCS/5-ASA significantly relieved DSS-induced colitis and enhanced the integrity of the intestinal epithelial barrier.

ES-IOCS/5-ASA also reduced the expression of NLRP3, ASC and IL-1β. Additionally, iron oxide nanoparticles used as nanozymes could alleviate inflammation. In summary, this study indicates that ES-IOCS/5-ASA exert anti-inflammatory effects on DSS-induced colitis by improving intestinal barrier function and inhibiting NLRP3 inflammasome expression, presenting a viable therapeutic choice for the treatment of UC.

Materials

5-ASA (purity≥98%) was obtained from TCI Development Co., Ltd. (Shanghai, China). Chitosan (medium molecular weight 200 kDa, 95% deacetylation degree) was purchased from Aladdin Chemistry Co., Ltd. (Shang, China). Sodium tripolyphosphate (TPP) was from Macklin Biochemical Technology Co., Ltd. (Shanghai, China). Meso-2,3-dimercaptosuccinic acid (DMSA)-modified IONPs (DMSA@IONPs, concentration 14.45 mg/mL) were provided by Nanoeast Biotechnology Co., Ltd. (Nanjing, China). Eudragit S100 by Evonik.

Dandan Zhang, Hao Wan, Ran Zhao, Yu Zhang, Hong Chen, Eudragit S100 coated iron oxide-chitosan nanocomposites for colon targeting of 5-aminosalicylic acid ameliorate ulcerative colitis by improving intestinal barrier function and inhibiting NLRP3 inflammasome, International Immunopharmacology, Volume 139, 2024, 112661, ISSN 1567-5769, https://doi.org/10.1016/j.intimp.2024.112661.