Effect of antioxidants on the stability of ONO-1301, a novel long-acting prostacyclin agonist, loaded in PLGA microspheres. (May 2013)

• Record Type: Journal Article
• Authors: Uchida, Takahiro; Hazekawa, Mai; Morisaki, Tomomi; Yoshida, Miyako; Sakai, Yoshiki
• Is Part Of: Journal of microencapsulation. Volume 30:Number 3(2013:May)
• Page Start: 245
• Page End: 256
• Publication Date: 2013-05
• Subjects: Microencapsulation -- Periodicals; Controlled release technology -- Periodicals; 615.19
• DOI: 10.3109/02652048.2012.720721
• Languages: English
• ISSNs: 0265-2048

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>in vitro</italic> 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.</p> </abstract>