Resveratrol (RES) is a nutraceutical with promising anti-inflammatory properties for the treatment of inflammatory bowel diseases (IBD). However, the clinical effectiveness of resveratrol as an oral anti-inflammatory agent is hindered by its extremely poor solubility and poor stability. In this study, we encapsulated resveratrol in β-lactoglobulin (BLG) nanospheres and systematically analyzed their formulation parameters in vitro followed by a thorough in vivo anti-inflammatory testing in a highly specialized spontaneous murine UC model (Winnie mice model). Complexation of resveratrol with BLG increased the aqueous solubility of resveratrol by ≈1.7 times with 10% w/w loading. Additionally, the in vitro dissolution of resveratrol from the particles was found to be higher compared to resveratrol alone, resulting in >90% resveratrol dissolution in ∼8 h. The anti-inflammatory activity of resveratrol was examined for the first time in Winnie mice, a mouse model that closely represents the clinical signs of IBD. At a 50 mg/kg oral dose for 2 weeks, BLG-RES significantly improved both % body weight and disease activity index (DAI), compared to free resveratrol in Winnie mice. Importantly, histological evaluations revealed a similar trend with striking improvement in the pathology of the colon via an increase in goblet cell numbers and recovery of colonic epithelium. BLG-RES significantly increased the expression level of cytokine interleukin-10 (Il10), which confirms the reduction in inflammation potentially because of the increased dissolution and stability of resveratrol by complexation with BLG. This comprehensive study demonstrates the effectiveness of biocompatible nanomaterials such as BLG in oral delivery of poorly soluble anti-inflammatory molecules such as resveratrol in the treatment of IBD.

中文翻译：

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β-乳球蛋白-纳米球包裹的白藜芦醇的口服给药可减轻患有自发性溃疡性结肠炎的 Winnie 小鼠的炎症

白藜芦醇 (RES) 是一种营养保健品，具有治疗炎症性肠病 (IBD) 的有希望的抗炎特性。然而，白藜芦醇作为口服抗炎剂的临床有效性受到其极差的溶解性和差的稳定性的阻碍。在这项研究中，我们将白藜芦醇封装在 β-乳球蛋白 (BLG) 纳米球中，并在体外系统地分析了它们的配方参数，然后在高度专业化的自发性小鼠 UC 模型（Winnie 小鼠模型）中进行了彻底的体内抗炎测试。白藜芦醇与 BLG 的络合使白藜芦醇的水溶性增加了约 1.7 倍，负载量为 10% w/w。此外，体外发现与单独的白藜芦醇相比，白藜芦醇从颗粒中的溶解度更高，导致在约 8 小时内溶解> 90% 的白藜芦醇。白藜芦醇的抗炎活性首次在 Winnie 小鼠身上进行了检测，这是一种非常接近 IBD 临床症状的小鼠模型。与 Winnie 小鼠中的游离白藜芦醇相比，BLG-RES 以 50 mg/kg 口服剂量给药 2 周，显着改善了体重百分比和疾病活动指数 (DAI)。重要的是，组织学评估揭示了类似的趋势，通过杯状细胞数量的增加和结肠上皮的恢复，结肠病理得到显着改善。BLG-RES 显着增加细胞因子白细胞介素 10（IL10)，这证实了炎症的减少可能是因为通过与 BLG 复合增加了白藜芦醇的溶解度和稳定性。这项综合研究证明了生物相容性纳米材料（如 BLG）在口服难溶性抗炎分子（如白藜芦醇）治疗 IBD 中的有效性。