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.