title: Cross-linked human serum albumin dimer has the potential for use as a plasma-retaining agent for the fatty acid-conjugated antidiabetic drugs.
abstract: OBJECTIVE
  The half-life of fatty acid-conjugated antidiabetic drugs are prolonged through binding to albumin, but this may not occur in diabetic patients with nephropathy complicated with hypoalbuminemia. We previously showed that human serum albumin (HSA) dimerized at the protein's Cys34 by 1,6-bis(maleimido)hexane has longer half-life than the monomer under high permeability conditions. The aim of this study was to investigate the superior ability of this HSA dimer as a plasma-retaining agent for fatty acid conjugated antidiabetic drugs.
  
  
  METHODS
  The diabetic nephropathy rat model was prepared by administering a single injection of streptozotocin (STZ) intravenously, and the pharmacokinetic properties of HSA monomer and dimer were evaluated. Site-specific fluorescent probe displacement experiments were performed using warfarin and dansylsarcosine as site I and site II specific fluorescent probes, respectively.
  
  
  RESULTS
  The half-life of the HSA dimer in STZ-induced diabetic nephropathy model rats was 1.5 times longer than the HSA monomer. The fluorescent probe displacement experiment results for HSA monomer and dimer were similar, where fatty acid-conjugated antidiabetic drugs displaced dansylsarcosine but not warfarin in a concentration-dependent manner.
  
  
  CONCLUSIONS
  The HSA dimer shows potential for use as a plasma-retaining agent for antidiabetic drugs due to its favourable pharmacokinetic properties.
authors.affiliation: Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Taguchi
authors.forename: Victor Tuan Giam
authors.initials: VT
authors.lastname: Chuang
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Yukino
authors.initials: Y
authors.lastname: Urata
authors.forename: Ryota
authors.initials: R
authors.lastname: Tanaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Anraku
authors.forename: Hakaru
authors.initials: H
authors.lastname: Seo
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kawai
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Komatsu
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
mesh_terms: D000818:Animals; D001665:Binding Sites; D003619:Dansyl Compounds / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy*; D019281:Dimerization; D004337:Drug Carriers; D005227:Fatty Acids / Q000737:chemistry; D005456:Fluorescent Dyes; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008301:Maleimides / Q000737:chemistry; D010539:Permeability; D010949:Plasma / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012521:Sarcosine / Q000031:analogs & derivatives / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry / Q000493:pharmacokinetics; D014859:Warfarin / Q000737:chemistry
chemical_list: D003619:Dansyl Compounds; D004337:Drug Carriers; D005227:Fatty Acids; D005456:Fluorescent Dyes; D007004:Hypoglycemic Agents; D008301:Maleimides; D012709:Serum Albumin; C037087:dansylsarcosine; C075594:1,6-bismaleimidohexane; D014859:Warfarin; D012521:Sarcosine
keywords: albumin; diabetes; fatty acid; glucagon like peptide-1 receptor agonist; insulin analogue