URAT1 and GLUT9 as drug targets in gout: progress in transporter-directed therapies and delivery technologies

Gout is a disorder of metabolism characterized by the deposition of urine crystals, and hyperuricemia, the treatment of which was uricosuric agent and xanthine oxidase inhibitor. Recently, attention has been paid to inhibitors of urate transporters, especially URAT1 and GLUT9, for the possibility of increasing uric acid excretion and decreasing serum uric acid levels in the last few years. The article discusses the physiological functions of URAT1 and GLUT9, genetic associations of these proteins with gout, and novel applications of drug delivery aimed at these proteins. This review comprises of clinical reports, and pharmacology updates regarding urate transporters and transport inhibitors. The role of genetic variants on the functioning of transporters were established and novel drug formulations were examined. The article discusses innovations in drug-delivery systems including sustained-release devices, liposomes, and nanoparticles to circumvent pharmacokinetic limitations and improve therapeutic efficacy. The advent of gene therapy and CRISPR editing for the modification of transporters could also be promising for the treatment of hyperuricemia. The integration of transporter-targeted therapy and new drug delivery systems may dramatically change the landscape of gout treatment in terms of safety and personalized treatment options.