Quercetin-Loaded Nanoparticles: A Promising Therapeutic Strategy for Inflammatory Bowel Disease.

Purpose: The aim of this study was to evaluate the characteristics and therapeutic efficacy of quercetin-loaded nanoparticles (NPs) using poly lactic-co-glycolic acid (PLGA) and Eudragit S100 (ES100) as carriers in the treatment of inflammatory bowel disease (IBD).

Materials and methods: Quercetin-loaded NPs were prepared using PLGA (QU-PLGA) and a combination of PLGA and ES100 (QU-PE). The mean particle sizes, encapsulation efficiencies, and stability of quercetin in aqueous solutions were assessed. Drug release profiles were evaluated under different pH conditions. In vitro studies involved cell endocytosis and cytotoxicity assays using Caco-2 and SW480 cells. In vivo efficacy was tested in dextran sulfate sodium (DSS) and oxazolone (OXA) induced acute colitis models in mice, with assessments including weight retention, colonic length, Murine Endoscopic Index of Colitis Severity (MEICS), histological scores, and inflammatory markers.

Results: Quercetin-loaded NPs (QU-PLGA: 160.4 ± 3.68 nm; QU-PE: 161.0 ± 2.30 nm) exhibited significantly smaller particle sizes compared to free quercetin (QU-Free: 2239 ± 404 nm) and high encapsulation efficiencies (87-90%). QU-PE showed pH-dependent release with improved stability in aqueous solutions. Quercetin-loaded NPs demonstrated enhanced cell membrane penetration and were non-toxic at tested concentrations. In the DSS and OXA colitis models, quercetin-loaded NPs significantly reduced disease severity, as evidenced by improved weight retention, longer colonic length, reduced MEICS and histological scores, decreased pro-inflammatory cytokines, and higher E-Cadherin expression compared to untreated groups. Notably, QU-PE demonstrated consistent anti-inflammatory effects across both models, with particularly pronounced efficacy in OXA-induced colitis, while QU-PLGA showed relatively superior therapeutic performance in the DSS model.

Conclusion: Quercetin-loaded NPs enhance the stability, bioavailability, and therapeutic efficacy of quercetin in IBD, offering a promising therapeutic strategy with superior physiological relevance for colitis treatment.