title: Biodistribution, hypouricemic efficacy and therapeutic mechanism of morin phospholipid complex loaded self-nanoemulsifying drug delivery systems in an experimental hyperuricemic model in rats.
abstract: OBJECTIVE
  This study aimed to compare the biodistribution and hypouricemic efficacy of morin and morin-phospholipid complex loaded self-nanoemulsifying drug delivery systems (MPC-SNEDDS), as well as to explore their therapeutic mechanisms.
  
  
  METHODS
  We studied the biodistribution of morin and MPC-SNEDDS after they were orally administered to rats. The hypouricemic efficacy and the therapeutic mechanisms of morin and MPC-SNEDDS were evaluated using potassium oxonate-induced hyperuricemic model in rats.
  
  
  RESULTS
  With enhanced morin concentration in liver and kidney, oral delivery of MPC-SNEDDS exhibited significantly stronger urate-lowering effect in hyperuricemic rats than morin. The hypouricemic efficacy of morin was due to reduced production of uric acid via inhibiting the mRNA expression of hepatic xanthine dehydrogenase/xanthine oxidase (XDH/XO), as well as decreased urate reabsorption via modulating the alteration of mRNA levels of glucose transporter (mGLUT9), renal organic anion transporter 1 (mOAT1) and uric acid transporter (mURAT1). MPC-SNEDDS dually inhibited mRNA expression and activity of hepatic XDH/XO and restored the dysregulation of renal mGLUT9, mOAT1 and mURAT1, contributing to its superior urate-lowering efficacy.
  
  
  CONCLUSIONS
  The results demonstrated the great potential of MPC-SNEDDS as an alternative oral strategy for active agents in treating hyperuricemia.
authors.affiliation: West China Hospital, Key Laboratory of Drug Targeting, Ministry of Education, Sichuan University, Chengdu, China.
authors.forename: Jinjie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: West China Hospital, Key Laboratory of Drug Targeting, Ministry of Education, Sichuan University, Chengdu, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Shuai
authors.affiliation: West China Hospital, Key Laboratory of Drug Targeting, Ministry of Education, Sichuan University, Chengdu, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Li
authors.affiliation: West China Hospital, Key Laboratory of Drug Targeting, Ministry of Education, Sichuan University, Chengdu, China.
authors.forename: Nanxi
authors.initials: N
authors.lastname: Xiang
authors.affiliation: West China Hospital, Key Laboratory of Drug Targeting, Ministry of Education, Sichuan University, Chengdu, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.affiliation: West China Hospital, Key Laboratory of Drug Targeting, Ministry of Education, Sichuan University, Chengdu, China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods; D005419:Flavonoids / Q000378:metabolism* / Q000494:pharmacology*; D033461:Hyperuricemia / Q000188:drug therapy* / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D049329:Nanostructures / Q000008:administration & dosage*; D027361:Organic Anion Transporters / Q000378:metabolism; D010743:Phospholipids / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution / Q000502:physiology*; D014527:Uric Acid / Q000378:metabolism; D047309:Flavones
chemical_list: D005419:Flavonoids; D027361:Organic Anion Transporters; D010743:Phospholipids; D014527:Uric Acid; C008548:morin; D047309:Flavones
keywords: hyperuricemic; morin phospholipid complex; renal organic ion transporter; self-nanoemulsifying drug delivery system; xanthine oxidase