Analysis and Testing Center, School of Pharmacy, Southwest Medical University, 1-1 Xianglin Road, Luzhou, 646000, Sichuan, People's Republic of China.
Laboratory of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, 646000, China.
J Nanobiotechnology. 2023 Aug 18;21(1):275. doi: 10.1186/s12951-023-02045-4.
Due to oral nano-delivery systems for the treatment of inflammatory bowel disease (IBD) are often failed to accumulated to the colonic site and could not achieve controlled drug release, it's urgent to develop a microenvironment responsive drug delivery to improve therapy efficacy. Inflammation at the IBD site is mainly mediated by macrophages, which are the key effector cells. Excessive inflammation leads to oxidative stress and intestinal mucosal damage. The use of curcumin (CUR) and emodin (EMO) together for the treatment of IBD is promising due to their respective anti-inflammatory and intestinal mucosal repair effects. In view of the pH gradient environment of gastrointestinal tract, here we prepared pH-responsive sodium alginate (SA) hydrogel-coated nanoemulsions to co-deliver CUR and EMO (CUR/EMO NE@SA) to achieve controlled drug release and specifically target macrophages of the colon.
In this study, a pH-responsive CUR/EMO NE@SA was successfully developed, in which the CUR/EMO NE was loaded by chitosan and further crosslinked with sodium alginate. CUR/EMO NE@SA had a pH-responsive property and could achieve controlled drug release in the colon. The preparation could significantly alleviate and improve the colon inflammatory microenvironment by decreasing TNF-α and IL-6 expression, increasing IL-10 expression, scavenging reactive oxygen species in macrophages, and by ameliorating the restoration of intestinal mucosal tight junction protein expression. Furthermore, we revealed the molecular mechanism of the preparation for IBD treatment, which might due to the CUR and EMO synergic inhibition of NF-κB to improve the pro-inflammatory microenvironment. Our study provides a new IBD therapy strategy via synergically inhibiting inflammatory, repairing mucosal and clearing ROS by pH-sensitive hydrogel-encapsulated nanoemulsion drug delivery system, which might be developed for other chronic inflammatory disease treatment.
It's suggested that pH-sensitive hydrogel-coated nanoemulsion-based codelivery systems are a promising combinatorial platform in IBD.
由于治疗炎症性肠病（IBD）的口服纳米递药系统往往无法积聚到结肠部位，也无法实现药物的控制释放，因此迫切需要开发一种微环境响应型药物递送系统以提高治疗效果。IBD 部位的炎症主要由巨噬细胞介导，巨噬细胞是关键的效应细胞。过度的炎症会导致氧化应激和肠道黏膜损伤。由于姜黄素（CUR）和大黄素（EMO）各自具有抗炎和肠道黏膜修复作用，因此联合使用 CUR 和 EMO 治疗 IBD 具有广阔的前景。鉴于胃肠道的 pH 梯度环境，我们在这里制备了 pH 响应性海藻酸钠（SA）水凝胶包被的纳米乳液，以共递送 CUR 和 EMO（CUR/EMO NE@SA），从而实现药物的控制释放，并靶向结肠中的巨噬细胞。
本研究成功开发了一种 pH 响应性 CUR/EMO NE@SA，其中 CUR/EMO NE 由壳聚糖装载，然后与海藻酸钠交联。CUR/EMO NE@SA 具有 pH 响应性，可以在结肠中实现药物的控制释放。该制剂通过降低 TNF-α 和 IL-6 的表达、增加 IL-10 的表达、清除巨噬细胞中的活性氧、改善肠道黏膜紧密连接蛋白表达的恢复，显著缓解和改善了结肠炎症微环境。此外，我们揭示了该制剂治疗 IBD 的分子机制，这可能是由于 CUR 和 EMO 协同抑制 NF-κB 以改善促炎微环境。我们的研究为通过 pH 敏感水凝胶包被的纳米乳液药物递送系统协同抑制炎症、修复黏膜和清除 ROS 提供了一种新的 IBD 治疗策略，该策略可能会应用于其他慢性炎症性疾病的治疗。
提示 pH 敏感水凝胶包被的纳米乳液共递药系统是治疗 IBD 的一种有前途的联合平台。
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