Microalgae-based drug delivery microspheres for treatment of hyperuricemia with renal injury

Abstract

Hyperuricemia is a common metabolic disease caused by an abnormally high level of uric acid (UA) due to excessive production or insufficient renal excretion, which progresses continuously and leads to severe kidney damage. In this study, an oral microsphere strategy (Eug/Lut@HAMA) was developed by encapsulating euglena (Eug) and luteolin (Lut) within methacrylated hyaluronic acid (HAMA) microspheres as a potential treatment for hyperuricemia with renal injury. Eug has UA adsorption capabilities, Lut aids in reducing UA formation, and HAMA microspheres possess adhesive properties. Eug/Lut@HAMA effectively reduced UA levels and provided protective effects against UA-induced reactive oxygen species production and cellular apoptosis. The microspheres demonstrated reduced gastric drug loss, prolonged intestinal retention, and sustained Eug and Lut release. Eug and Lut exhibit complementarity in the treatment of acute/chronic hyperuricemia, with Eug increasing UA excretion and Lut decreasing UA production. Eug/Lut@HAMA offered multiple benefits in improving renal injury, including anti-inflammatory, antioxidant, and anti-fibrotic properties. Additionally, Eug/Lut@HAMA demonstrated long-term biosafety for oral administration. This study presents a novel, effective, and safe approach to managing acute/chronic hyperuricemia with renal injury by reducing UA production and enhancing UA excretion.