Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model

International Journal of Molecular Sciences

Noriaki Nagai²  Chiaki Yoshioka²  Yoshimasa Ito¹  Yoshinori Funakami²  Hiroyuki Nishikawa²  Atsufumi Kawabata² 

[1] Faculty of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan

关键词: cilostazol;    ischemic stroke;    injection formulation;    nanoparticles;    pharmacokinetics;   

DOI  :  10.3390/ijms161226166

来源: mdpi

【 摘 要 】

It was reported that cilostazol (CLZ) suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZ_nano dispersion; particle size 81 ± 59 nm, mean ± S.D.), and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice). The pharmacokinetics of injections of CLZ_nano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZ_nano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZ_nano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZ_nano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZ_nano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.