An oral polyphenol host-guest nanoparticle for targeted therapy of inflammatory bowel disease

炎症性肠病 单宁酸 药理学 药物输送 药品 体内 靶向给药 医学 多酚 结肠炎 活性氧 疾病 化学 抗氧化剂 免疫学 材料科学 纳米技术 生物 生物化学 病理 有机化学 生物技术
作者
Chong Zhang,Fen Zeng,Zhengyang Fan,Zhen He,Liang Tai,Qiang Peng,Yixin Zhang,Zhenhua Chao,Wenning Jiang,Lingyun Jia,Lulu Han
出处
期刊:Acta Biomaterialia [Elsevier BV]
卷期号:169: 422-433 被引量:18
标识
DOI:10.1016/j.actbio.2023.08.020
摘要

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.
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