SKL of Marine Food Processing & Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China.
College of Biosystems Engineering and Food Science, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, China.
Int J Pharm. 2023 Nov 5;646:123496. doi: 10.1016/j.ijpharm.2023.123496. Epub 2023 Oct 6.
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.
开发用于植物化学物质口服给药的创新策略为解决肠道疾病提供了一个有前途的方法。然而，仍然存在许多挑战，包括有限的治疗效果、低生物利用度和不足的生物相容性。在这项研究中，我们使用交联环糊精-金属有机骨架（CDF）来包封白藜芦醇（Res），生成 Res-CDF，随后将其纳入天然多糖水凝胶微球（Res-CDF in MPs）中，以实现靶向口服给药，缓解溃疡性结肠炎（UC）。分子动力学模拟阐明了 Res 被γ-CD 吸附的潜在机制。重要的是，Res-CDF in MPs 配方可防止胃酸降解，同时保持 Res 的生物活性。此外，该设计可使 Res-CDF 特异性地在肠道的微碱性环境中释放，随后持续释放 Res。在 UC 小鼠模型中，Res-CDF in MPs 通过减轻促炎细胞因子的产生表现出强大的抗炎作用，并表现出抗氧化特性。此外，Res-CDF in MPs 增强了紧密连接蛋白 ZO-1、Occludin 和粘蛋白-2（Muc-2）的表达，从而维持了正常的肠道屏障功能。这种创新的口服给药策略利用了多糖水凝胶和 CDF 的优势来提高植物化学物质的生物利用度，为开发利用天然植物化学物质治疗肠道相关疾病的新型口服干预措施奠定了基础。
