title: Effect of antioxidants on the stability of ONO-1301, a novel long-acting prostacyclin agonist, loaded in PLGA microspheres.
abstract: The purpose of this study was to investigate the physicochemical stability of ONO-1301 in poly(lactide-co-glycolide) microspheres (PLGA MS) under storage for 28 days in the absence or presence of butylated hydroxytoluene (BHT) or α-tocopherol as antioxidant. First, we observed the hydrolysed product: (i) in acidic solution and oxidized product and (ii) in PLGA MS under storage in HPLC study, each structure was determined by liquid chromatography-nuclear magnetic resonance/mass spectrometry. Second, ONO-1301-loaded PLGA MS containing 10% BHT was shown to be superior to ONO-1301-loaded PLGA MS without BHT, in the standpoint of the stability under storage or in vitro drug-release test, and AUC(0-28) following subcutaneous injection in rats. Finally, ONO-1301-loaded PLGA MS with 10% BHT were demonstrated to be significantly more effective than ONO-1301-loaded PLGA MS without BHT in a murine sponge model of angiogenesis. In conclusion, BHT is an effective antioxidant on the stability of ONO-1301 in PLGA MS under storage.
authors.affiliation: Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya-shi, Hyogo, Japan. takahiro@mukogawa-u.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Uchida
authors.forename: Mai
authors.initials: M
authors.lastname: Hazekawa
authors.forename: Tomomi
authors.initials: T
authors.lastname: Morisaki
authors.forename: Miyako
authors.initials: M
authors.lastname: Yoshida
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sakai
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002853:Chromatography, Liquid; D019344:Lactic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D044062:Prostaglandins I / Q000819:agonists*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D044062:Prostaglandins I; D011725:Pyridines; C105488:ONO 1301; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid