Wang Wenpeng, Li Mingrui, Liu Ying, Weigmann Benno
Medical Clinic I, Kussmaul Campus for Medical Research, University of Erlangen-Nürnberg, Erlangen, Germany.
Department 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.
J Inflamm Res. 2025 Sep 10;18:12447-12461. doi: 10.2147/JIR.S545203. eCollection 2025.
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).
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.
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.
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.
本研究旨在评估以聚乳酸-羟基乙酸共聚物（PLGA）和聚丙烯酸树脂S100（ES100）为载体的槲皮素纳米颗粒（NPs）在治疗炎症性肠病（IBD）中的特性和治疗效果。
使用PLGA制备载槲皮素纳米颗粒（QU-PLGA）以及PLGA与ES100的组合制备载槲皮素纳米颗粒（QU-PE）。评估了槲皮素在水溶液中的平均粒径、包封率和稳定性。在不同pH条件下评估药物释放曲线。体外研究包括使用Caco-2和SW480细胞进行细胞内吞和细胞毒性测定。在葡聚糖硫酸钠（DSS）和恶唑酮（OXA）诱导的小鼠急性结肠炎模型中测试体内疗效，评估包括体重维持、结肠长度、小鼠结肠炎严重程度内镜指数（MEICS）、组织学评分和炎症标志物。
与游离槲皮素（QU-Free：2239±404 nm）相比，载槲皮素纳米颗粒（QU-PLGA：160.4±3.68 nm；QU-PE：161.0±2.30 nm）的粒径显著更小，且包封率高（87-90%）。QU-PE表现出pH依赖性释放，在水溶液中的稳定性有所提高。载槲皮素纳米颗粒表现出增强的细胞膜穿透性，在测试浓度下无毒。在DSS和OXA结肠炎模型中，载槲皮素纳米颗粒显著降低了疾病严重程度，与未治疗组相比，体重维持改善、结肠长度更长、MEICS和组织学评分降低、促炎细胞因子减少以及E-钙黏蛋白表达升高证明了这一点。值得注意的是，QU-PE在两种模型中均表现出一致的抗炎作用，在OXA诱导的结肠炎中疗效尤为显著，而QU-PLGA在DSS模型中表现出相对更优的治疗性能。
载槲皮素纳米颗粒提高了槲皮素在IBD中的稳定性、生物利用度和治疗效果，为结肠炎治疗提供了一种具有卓越生理相关性的有前景的治疗策略。
