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

Autor: Noriaki Nagai, Hiroyuki Nishikawa, Atsufumi Kawabata, Yoshimasa Ito, Yoshinori Funakami, Chiaki Yoshioka
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 16, Iss 12, Pp 29329-29344 (2015)
International Journal of Molecular Sciences
Volume 16
Issue 12
Pages 29329-29344
International Journal of Molecular Sciences; Volume 16; Issue 12; Pages: 29329-29344
ISSN: 1422-0067
Popis: 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 (CLZnano 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 CLZnano 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 CLZnano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZnano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZnano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZnano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage.
Databáze: OpenAIRE