Liaoning Key Laboratory of Molecular Recognition and Imaging, School of Bioengineering, Dalian University of Technology, Dalian 116023, PR China.
Liaoning Key Laboratory of Molecular Recognition and Imaging, School of Bioengineering, Dalian University of Technology, Dalian 116023, PR China.
Acta Biomater. 2023 Oct 1;169:422-433. doi: 10.1016/j.actbio.2023.08.020. Epub 2023 Aug 18.
Inflammatory bowel disease (IBD) is a global public health challenge that affects millions of people. Current medical treatments for IBD are not fully effective and may cause undesirable side effects on patients. Thus, there is an urgent need for safe, simple, and efficacious strategies to treat IBD in clinical settings. Here, we develop an oral polyphenol nanoparticle (PDT) by assembling dexamethasone sodium phosphate (DSP)-loaded poly-β-cyclodextrin with tannic acid via host-guest interactions for treating IBD. This one-step assembly process is rapid (within 10 s), reproducible, and free of harmful chemical agents, which can facilitate its clinical translation. PDT is negatively charged due to the three components, which enable it to specifically target the positively charged inflamed colonic mucosa through electrostatic attraction, thus localizing the drug at the inflamed site to reduce systemic exposure and side effects. Furthermore, PDT exhibits a strong reactive oxygen species (ROS)-scavenging ability derived from the tannic acid component, which can alleviate ROS-mediated inflammatory responses and ameliorate IBD symptoms. Compared with free DSP, PDT demonstrates sustained DSP release behavior in vitro and in vivo, as well as enhanced therapeutic efficacy in a colitis mouse model. These results suggest that PDT might be a potential therapeutic agent for the treatment of IBD. Moreover, this facile polyphenol host-guest assembly strategy may provide a promising drug-delivery platform for treating various diseases STATEMENT OF SIGNIFICANCE: To develop safe and effective treatments for inflammatory bowel disease (IBD), we have designed an oral polyphenol nanoparticle (PDT) using the host-guest assembly of dexamethasone sodium phosphate (DSP)-loaded poly-β-cyclodextrin with tannic acid. Through in vitro and in vivo experiments, PDT has demonstrated remarkable inflammation-targeting, ROS-scavenging, and anti-inflammatory properties, along with sustained release of DSP. Moreover, in an IBD mouse model, PDT has shown significantly improved therapeutic efficacy compared to free DSP. The host-guest assembly strategy employed for PDT is noteworthy for its rapidity, reproducibility, and safety due to the absence of harmful chemicals, holding great promise for designing a diverse range of nanomedicines customized for treating various diseases.
炎症性肠病（IBD）是一项全球性的公共健康挑战，影响着数以百万计的人群。目前针对 IBD 的医疗方法并非完全有效，且可能会给患者带来不良的副作用。因此，临床上迫切需要安全、简便、有效的治疗 IBD 的策略。在这里，我们通过主客体相互作用将负载地塞米松磷酸钠（DSP）的聚-β-环糊精与单宁酸组装成一种口服多酚纳米颗粒（PDT）来治疗 IBD。这种一步组装过程快速（在 10 秒内）、可重现且无有害化学试剂，有利于其临床转化。由于三个组成部分的存在，PDT 带负电荷，使其能够通过静电吸引特异性靶向带正电荷的发炎结肠黏膜，从而将药物定位在发炎部位，减少全身暴露和副作用。此外，PDT 具有来自单宁酸部分的强活性氧（ROS）清除能力，可以减轻 ROS 介导的炎症反应并改善 IBD 症状。与游离 DSP 相比，PDT 在体外和体内均表现出持续的 DSP 释放行为，并在结肠炎小鼠模型中增强了治疗效果。这些结果表明 PDT 可能是治疗 IBD 的一种有潜力的治疗剂。此外，这种简便的多酚主客体组装策略可能为治疗各种疾病提供一种有前途的药物递送平台。
