Fucoidan/chitosan coated nanoliposomes enhancing URAT1 targeting of rutin for alleviating hyperuricemia

Urate transporter 1 (URAT1), a principal transporter responsible for urate reabsorption, has emerged as a promising target for hyperuricemia. Discovery and development of safe and effective URAT1 inhibitors are urgently needed. Herein, our screening identified rutin, a flavonoid compound, as a potent inhibitor of URAT1, exhibiting high binding affinity (-9.803 kcal/mol) and low cytotoxicity. Notably, the binding energy of rutin-URAT1 complex was -60.66 kcal/mol, approximately 2.87-fold greater than that of uric acid. However, the bioavailability of rutin is considerably restricted due to the high hydrophobicity, and thereby low targeting ability. To improve the targeting of rutin, fucoidan/chitosan-coated rutin-nanoliposome (FC-RNL) was prepared for ruitn delivery. In vivo results indicated that FC-RNL significantly reduced serum uric acid level by inhibiting URAT1 and improved renal function. Moreover, FC-RNL reduced the inflammatory factors levels in both serum and renal tissue by inhibition of the activation of NF-κB/NLRP3 signaling pathway. Collectively, FC-RNL, a promising nanocarrier for rutin delivery, demonstrated potential to alleviate hyperuricemia by enhancing URAT1 targeting and reducing inflammation, thereby providing insights into the development of urate-lowering functional foods.