Wenpeng Wang,1,2,* Mingrui Li,1,3,* Ying Liu,1,* Benno Weigmann1,4 

1Medical Clinic I, Kussmaul Campus for Medical Research, University of Erlangen-Nürnberg, Erlangen, Germany; 2Department of Colorectal Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, People’s Republic of China; 3Department of Endocrinology, Dazhou Central Hospital, Dazhou, People’s Republic of China; 4FAU Profile Center Immunomedicine, University of Erlangen-Nürnberg, Erlangen, Germany

*These authors contributed equally to this work

Correspondence: Benno Weigmann, Medical Clinic I, Kussmaul Campus for Medical Research, University of Erlangen-Nürnberg, Hartmannstr.14, Erlangen, 91052, Germany, Tel +49 9131 85-35885, Fax +49 9131 85-355959, Email benno.weigmann@uk-erlangen.de

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.

Keywords: quercetin, nanoparticles, poly lactic-co-glycolic acid, PLGA, Eudragit S100, inflammatory bowel disease, therapeutic efficacy