Preparation and characterization of colon targeted Carboxymethyl inulin-sulfadiazine conjugated pellets, coated with Eudragit to alleviate the severity of ulcerative colitis in albino rats

Abstract

Among major complications of ulcerative colitis (UC), gut microbiota dysbiosis and chronic inflammation remain challenging for the pharmaceutical scientists, which can be addressed by a prebiotic-assisted antimicrobial system. An attempt has been made to synthesize a novel complex of Carboxymethyl Inulin-Sulfadiazine (CMI-SDZ) loaded sustained release (SR) pellets for targeted therapy of UC. Formation of CMI-SDZ was confirmed by FTIR and its crystallinity was revealed by XRD. DPPH antioxidant assay proved 70 % scavenging activity which was also further confirmed by reducing power assay. The prebiotic nature of CMI-SDZ was confirmed for L. rhamnosus with enhanced antimicrobial activity against E. coli, S. aureus and C. albicans compared to SDZ alone. SR pellets of CMI, SDZ and CMI-SDZ were prepared using Eudragit-L100 and coated with a mixture of Inulin-Eudragit RS-100 for targeted delivery in colon. In-vitro % drug release optimized formulations C-P1-CMI, C-P1-SDZ and C-P1-CMI-SDZ in a simulated colon fluid over a period of 10 h were 75, 84 and 79 %, respectively. Acetic acid (AA) induced UC rat model was used to test UC treatment efficacy by assessing colitis activity index (CAI) score, histopathology of rat colon tissue, oxidative stress and inflammatory markers. Treatment with C-P1-CMI-SDZ increased levels of anti-inflammatory cytokine (IL-10) and antioxidant enzyme (GSH-Px), while reducing levels of inflammatory biomarkers (IL-6, IL-1β, TNF-α, MPO, MDA and iNOS). Conclusively, C-P1-CMI-SDZ can be considered a promising candidate to prevent dysbiosis and colon inflammation associated with UC.

Keywords: Antioxidant activity; Carboxymethyl inulin; Sulfadiazine; Ulcerative colitis.