Intestine-Targeted Explosive Hydrogel Microsphere Promotes Uric Acid Excretion for Gout Therapy,Advanced Materials

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Intestine-Targeted Explosive Hydrogel Microsphere Promotes Uric Acid Excretion for Gout Therapy
Advanced Materials ( IF 27.4 ) Pub Date : 2023-11-23 , DOI: 10.1002/adma.202310492
Yunkai Tang ₁ , Yawei Du ₁ , Junna Ye ₂ , Lianfu Deng ₁ , Wenguo Cui ₁

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Uric acid metabolism disorder triggers metabolic diseases, especially gout. However, increasing uric acid excretion remains a challenge. Here, an accelerative uric acid excretion pathway via an oral intestine-explosive hydrogel microsphere merely containing uricase and dopamine is reported. After oral administration, uricase is exposed and immobilized on intestinal mucosa along with an in situ dopamine polymerization via a cascade reaction triggered by the intestinal specific environment. By this means, trace amount of uricase is required to in situ up-regulate uric acid transporter proteins of intestinal epithelial cells, causing accelerated intestinal uric acid excretion. From in vitro data, the uric acid in fecal samples from gout patients could be significantly reduced by up to 37% by the mimic mucosa-immobilized uricase on the isolated porcine tissues. Both hyperuricemia and acute gouty arthritis in vivo mouse models confirm the uric acid excretion efficacy of intestine-explosive hydrogel microspheres. Fecal uric acid excretion is increased around 30% and blood uric acid is reduced more than 70%. In addition, 16S ribosomal RNA sequencing showed that the microspheres optimized intestinal flora composition as well. In conclusion, a unique pathway via the intestine in situ regulation to realize an efficient uric acid intestinal excretion for gout therapy is developed.

中文翻译：

肠道靶向爆炸性水凝胶微球促进尿酸排泄用于痛风治疗

尿酸代谢紊乱会引发代谢性疾病，尤其是痛风。然而，增加尿酸排泄仍然是一个挑战。在此，报道了通过仅含有尿酸酶和多巴胺的口服肠爆炸性水凝胶微球的加速尿酸排泄途径。口服给药后，尿酸酶暴露并固定在肠粘膜上，并通过肠道特定环境引发的级联反应发生原位多巴胺聚合。通过这种方式，需要微量尿酸酶原位上调肠上皮细胞的尿酸转运蛋白，从而加速肠道尿酸排泄。从体外数据来看，在分离的猪组织上模拟粘膜固定尿酸酶可将痛风患者粪便样本中的尿酸显着降低高达37%。高尿酸血症和急性痛风性关节炎体内小鼠模型均证实了肠爆水凝胶微球的尿酸排泄功效。粪尿酸排泄增加30%左右，血尿酸降低70%以上。此外，16S核糖体RNA测序表明微球还优化了肠道菌群组成。总之，开发了一种通过肠道原位调节实现尿酸肠道有效排泄的独特途径，用于痛风治疗。

更新日期：2023-11-23

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