Single injection of ONO-1301-loaded PLGA microspheres directly after ischaemia reduces ischaemic damage in rats subjected to middle cerebral artery occlusion.

Abstract

OBJECTIVES:

ONO-1301 was developed as a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. In this study, we investigated the therapeutic time window of oral ONO-1301 and the effect of a single subcutaneous injection of ONO-1301-loaded poly(lactide-co-glycolide) (PLGA) microspheres (ONO-1301 PLGA MS) on infarction volume, functional deficits and plasma ONO-1301 levels following a 1 h middle cerebral artery occlusion (MCAO) in rats.

METHODS:

Rats were treated with ONO-1301 (3 mg/kg) orally twice-daily starting 1 (directly), 6 or 24 h after MCAO. Rats received a single subcutaneous injection of ONO-1301 PLGA MS (10 mg/kg) directly after MCAO. Neurological scores were evaluated directly after, 1 and 6 h, 1, 2, and 3 days after MCAO. Infarct volume, oedema and plasma ONO-1301 levels were measured three days after MCAO.

KEY FINDINGS:

Neurological scores, oedema and infarct volume were all significantly improved in rats repeatedly treated with oral ONO-1301 and subcutaneous ONO-1301 PLGA MS directly after MCAO. Plasma ONO-1301 levels were significantly lower in rats treated directly after MCAO (either with ONO-1301 or ONO-1301 PLGA MS) than in rats treated 6 h or 24 h after MCAO.

CONCLUSIONS:

ONO-1301 PLGA MS subcutaneous treatment directly after MCAO showed a neuroprotective effect as well as oral ONO-1301. This treatment should be clinically more convenient than ONO-1301 oral administration since it is delivered as a single treatment after MCAO.

• Authors: Mai Hazekawa, Yoshiki Sakai, Miyako Yoshida, Tamami Haraguchi, Takahiro Uchida
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 64 Issue 3 Pg. 353-9 (Mar 2012) ISSN: 2042-7158 [Electronic] England
• PMID: 22309267 (Publication Type: Journal Article)
• Copyright: © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

Chemical References

• Biocompatible Materials
• Neuroprotective Agents
• Pyridines
• ONO 1301
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Epoprostenol
• Thromboxane-A Synthase

Topics

• Animals
• Biocompatible Materials (therapeutic use)
• Epoprostenol (agonists)
• Infarction, Middle Cerebral Artery (complications)
• Injections, Subcutaneous
• Lactic Acid (therapeutic use)
• Male
• Microspheres
• Neuroprotective Agents (therapeutic use)
• Polyglycolic Acid (therapeutic use)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Pyridines (therapeutic use)
• Rats
• Rats, Wistar
• Reperfusion Injury (etiology, prevention & control)
• Statistics as Topic
• Thromboxane-A Synthase (antagonists & inhibitors)
• Time Factors