Volume 64, Issue 3 pp. 353-359

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

Mai Hazekawa,

Mai Hazekawa

Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo

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Yoshiki Sakai,

Yoshiki Sakai

Ono Pharmaceutical Co., Ltd, Research Headquarters, Osaka, Japan

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Miyako Yoshida,

Miyako Yoshida

Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo

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Tamami Haraguchi,

Tamami Haraguchi

Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo

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Takahiro Uchida,

Corresponding Author

Takahiro Uchida

Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo

Takahiro Uchida, Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, 11-68, 9-Bancho, Koshien, Nishinomiya-shi, Hyogo, 663-8179, Japan. E-mail: [email protected]Search for more papers by this author

Mai Hazekawa,

Mai Hazekawa

Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo

Search for more papers by this author

Yoshiki Sakai,

Yoshiki Sakai

Ono Pharmaceutical Co., Ltd, Research Headquarters, Osaka, Japan

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Miyako Yoshida,

Miyako Yoshida

Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo

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Tamami Haraguchi,

Tamami Haraguchi

Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo

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Takahiro Uchida,

Corresponding Author

Takahiro Uchida

Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo

First published: 07 December 2011

https://doi.org/10.1111/j.2042-7158.2011.01416.x

Citations: 16

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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.

References

1 Tanouchi T et al. Highly selective inhibitors of thromboxane synthetase. 2 Pyridine derivatives. J Med Chem 1981; 24: 1149–1155.
10.1021/jm00142a006
CAS PubMed Web of Science® Google Scholar
2 Kataoka M et al. A long-acting prostacyclin agonist with thromboxane inhibitory activity for pulmonary hypertension. Am J Respir Crit Care Med 2005; 172: 1575–1580.
10.1164/rccm.200501-102OC
PubMed Web of Science® Google Scholar
3 Obata H et al. Single injection of a sustained-release prostacyclin analog improves pulmonary hypertension in rats. Am J Respir Crit Care Med 2008; 177: 195–201.
10.1164/rccm.200703-349OC
CAS PubMed Web of Science® Google Scholar
4 Murakami S et al. Prostacyclin agonist with thromboxane synthase inhibitory activity (ONO-1301) attenuates bleomycin-induced pulmonary fibrosis in mice. Am J Physiol Lung Cell Mol Physiol 2006; 290: 59–65.
10.1152/ajplung.00042.2005
CAS PubMed Web of Science® Google Scholar
5 Okano Y et al. Orally active prostacyclin analogue in primary pulmonary hypertension. Lancet 1997; 349: 1365.
10.1016/S0140-6736(97)24019-5
CAS PubMed Web of Science® Google Scholar
6 Nagaya N et al. Effect of orally active prostacyclin analogue on survival of outpatients with primary pulmonary hypertension. J Am Coll Cardiol 1999; 34: 1188–1192.
10.1016/S0735-1097(99)00312-5
CAS PubMed Web of Science® Google Scholar
7 Olschewski H et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 2002; 347: 322–329.
10.1056/NEJMoa020204
CAS PubMed Web of Science® Google Scholar
8 Simonneau G et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary hypertension: a double-blind randomized controlled trial. Am J Respir Crit Care Med 2002; 165: 800–804.
10.1164/ajrccm.165.6.2106079
PubMed Web of Science® Google Scholar
9 Ike O et al. Biodegradation and antitumour effect of adriamycin-contapoly (L-lactic acid) microspheres. Biomaterials 1991; 12: 757–762.
10.1016/0142-9612(91)90026-7
CAS PubMed Web of Science® Google Scholar
10 Umeki N et al. Preparation and evaluation of biodegradable microspheres containing a new potent osteogenic compound and new synthetic polymers for sustained release. Int J Pharm 2010; 392: 42–50.
10.1016/j.ijpharm.2010.03.020
CAS PubMed Web of Science® Google Scholar
11 Grände PO et al. Low-dose prostacyclin in treatment of severe brain trauma evaluated with microdialysis and jugular bulb oxygen measurements. Acta Anaesthesiol Scand 2000; 44: 886–894.
10.1034/j.1399-6576.2000.440718.x
CAS PubMed Web of Science® Google Scholar
12 Naredi S et al. An outcome study of severe traumatic head injury using the ‘Lund therapy’ with low-dose prostacyclin. Acta Anaethesiol. Scand. 2001; 45: 402–426.
10.1034/j.1399-6576.2001.045004402.x
CAS PubMed Web of Science® Google Scholar
13 Ginsberg MD. Adventures in the pathophysiology of brain ischemia: penumbra, gene expression, neuroprotection: the 2002 Thomas Willis Lecture. Stroke 2003; 34: 214–223.
10.1161/01.STR.0000048846.09677.62
PubMed Web of Science® Google Scholar
14 Belayev L et al. Middle cerebral artery occlusion in the rat by intraluminal suture: neurological and pathological evaluation of an improved model. Stroke 1996; 27: 1616–1623.
10.1161/01.STR.27.9.1616
CAS PubMed Web of Science® Google Scholar
15 Hayakawa K et al. Delayed treatment with minocycline ameliorates neurologic impairment through activated microglia expressing a high-mobility group box1-inhibiting mechanism. Stroke 2008; 39: 951–958.
10.1161/STROKEAHA.107.495820
CAS PubMed Web of Science® Google Scholar
16 Hazekawa M et al. Preparation of ONO-1301-loaded PLGA microspheres and their effect on nerve conduction velocity. J Pharm Pharmacol 2011; 63: 362–368.
10.1111/j.2042-7158.2010.01237.x
CAS PubMed Web of Science® Google Scholar
17 Yamamoto M et al. Behavioral changes after focal cerebral ischemia by left middle cerebral artery occlusion in rats. Brain Res 1988; 452: 323–328.
10.1016/0006-8993(88)90036-4
PubMed Web of Science® Google Scholar
18 Tamura A et al. Focal cerebral ischemia in the rat. 1: Description of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cereb Blood Flow Metab 1981; 1: 53–60.
10.1038/jcbfm.1981.6
CAS PubMed Web of Science® Google Scholar
19 Choi JM et al. Neuroprotective effect of cilostazol against focal cerebral ischemia via antiapoptotic action in rats. J Pharmacol Exp Ther 2002; 300: 787–793.
10.1124/jpet.300.3.787
CAS PubMed Web of Science® Google Scholar
20 Xing B et al. Ischemic post-conditioning protects brain and reduces inflammation in a rat model of focal cerebral ischemia/reperfusion. J Neurochem 2008; 105: 1737–1745.
10.1111/j.1471-4159.2008.05276.x
CAS PubMed Web of Science® Google Scholar
21 Pinto E et al. Feasibility of localized immunosuppressioon: 2. PLA microspheres for the sustained local delivery of a soft immunosuppressant. Phatmazie 2010; 65: 429–435.
CAS PubMed Web of Science® Google Scholar
22 Yoshikawa N. Relationship between standing balance and symmetry measurements in patients following recent strokes (3 weeks) or older strokes (6 months). Rigaku Ryoho Janaru 2005; 39: 199–199.
Google Scholar
23 Chao X et al. Neuroprotective effect of osthole against acute ischemic stroke on middle cerebral ischemia occlusion in rats. Brain Res 2010; 1363: 206–211.
10.1016/j.brainres.2010.09.052
CAS PubMed Web of Science® Google Scholar
24 McCabe C et al. Differences in the evolution of the ischemic penumbra in stroke-prone spontaneously hypertensive and Wistar-Kyoto rats. Stroke 2009; 40: 3864–3868.
10.1161/STROKEAHA.109.559021
PubMed Web of Science® Google Scholar
25 Reinstrup P, Nordström CH. Prostacyclin infusion may prevent secondary damage in precontusional brain tissue. Neurocrit Care 2011; 14: 441–446.
10.1007/s12028-010-9486-3
CAS PubMed Web of Science® Google Scholar
26 Lipton P. Ischemic cell death in brain neurons. Physiol Rev 1999; 79: 1431–1568.
10.1152/physrev.1999.79.4.1431
CAS PubMed Web of Science® Google Scholar

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Volume64, Issue3

March 2012

Pages 353-359

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

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

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