Efficient oral delivery of resveratrol-loaded cyclodextrin-metal organic framework for alleviation of ulcerative colitis

Developing innovative strategies for the oral administration of phytochemicals presents a promising approach to addressing intestinal diseases. However, numerous challenges persist, including limited therapeutic efficacy, poor bioavailability, and inadequate biocompatibility. In this study, we employed a cross-linked cyclodextrin-metal organic framework (CDF) to encapsulate resveratrol (Res), generating Res-CDF, which was subsequently incorporated into natural polysaccharide hydrogel microspheres (Res-CDF in MPs) for targeted oral delivery to alleviate ulcerative colitis (UC). The underlying adsorption mechanism of Res by γ-CD elucidated by molecular dynamics simulations. Importantly, the Res-CDF in MPs formulation protected against gastric acid degradation while preserving the bioactivity of Res. Moreover, the design enabled specific release of Res-CDF in response to the mildly alkaline environment of the intestinal tract, followed by sustained Res release. In UC mice model, Res-CDF in MPs demonstrated potent anti-inflammatory effects by attenuating pro-inflammatory cytokine production and exhibited antioxidant properties. Additionally, Res-CDF in MPs enhanced the expression of tight junction proteins ZO-1, Occludin, and mucin-2 (Muc-2), thereby maintaining normal intestinal barrier function. This innovative oral delivery strategy capitalizes on the advantageous properties of polysaccharide hydrogel and CDF to augment bioavailability of phytochemicals, laying the groundwork for developing novel oral interventions employing natural phytochemicals to address intestinal-related diseases.