title: Preparation of ONO-1301-loaded poly(lactide-co-glycolide) microspheres and their effect on nerve conduction velocity.
abstract: OBJECTIVE
  The aim of this study was to prepare poly(lactide-co-glycolide) (PLGA) microspheres containing ONO-1301, a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity, with 10% of drug released in the initial burst and a sustained-release period of about 3 weeks after administration. The effect of PLGA type (molecular weight and the lactide/glycolide (L/G) ratio in PLGA), the preparative conditions and the particle size on the in-vitro release profile were examined. The effect of optimized ONO-1301-loaded PLGA microspheres on delayed nerve condition velocity (NCV) was investigated in streptozotocin (STZ) induced diabetic rats.
  
  
  METHODS
  ONO-1301 PLGA microspheres were produced by the oil-in-water emulsion/solvent evaporation method. Drug release from the prepared microspheres was monitored in phosphate buffer solution at 37°C for 4 weeks by high-performance liquid chromatography. The in-vivo study was performed in STZ-induced diabetic rats treated with optimized ONO-1301 PLGA microspheres (10 mg/kg by intramuscular or subcutaneous injection every 3 weeks). NCV was measured in the thigh 4, 8 and 12 weeks after induction.
  
  
  RESULTS
  The molecular weights of PLGA, the L/G ratio in PLGA and the particle diameter all affected the length of the sustained release period. Drug release from microspheres containing PLGA 5050 (MW 50,000, L/G 50/50), with an average diameter of about 30 µm, could be sustained for 3 weeks in vitro. In the in-vivo study, delayed NCV was significantly increased by treatment with these ONO-1301 PLGA microspheres once every 3 weeks, in comparison with vehicle only.
  
  
  CONCLUSIONS
  Local intramuscular injection of sustained-release ONO-1301 PLGA microspheres improved delayed NCV in STZ-induced diabetic rats.
authors.affiliation: Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Hazekawa
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sakai
authors.forename: Miyako
authors.initials: M
authors.lastname: Yoshida
authors.forename: Tamami
authors.initials: T
authors.lastname: Haraguchi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Morisaki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Uchida
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D004337:Drug Carriers; D005260:Female; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D008970:Molecular Weight; D009431:Neural Conduction / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011725:Pyridines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
chemical_list: D004337:Drug Carriers; D011725:Pyridines; C105488:ONO 1301; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid