Oral Delivery of β-Lactoglobulin-Nanosphere-Encapsulated Resveratrol Alleviates Inflammation in Winnie Mice with Spontaneous Ulcerative Colitis

Abstract

Resveratrol (RES) is a nutraceutical with promising anti-inflammatory properties for the treatment of inflammatory bowel diseases (IBD) including colitis and ulcerative colitis (UC). 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, in-vitro dissolution of resveratrol from the particles was found to be higher compared to resveratrol alone, which was further enhanced in the presence of intestinal enzymes resulting > 90% resveratrol dissolution in ~ 8 hours. 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 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 pathology of the colon via increase in goblet cell numbers and recovery of colonic epithelium. BLG-RES significantly increased expression level of cytokine interlukin-10 (Il10) confirming a greater reduction in inflammation potentially due to increased dissolution and stability of resveratrol by complexation with BLG. This comprehensive study demonstrates effectiveness of biocompatible nanomaterials such as BLG in oral delivery of poorly soluble anti-inflammatory molecules such as resveratrol in the treatment of IBD.