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 |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Male
Ischemia Tetrazoles Blood Pressure cilostazol ischemic stroke injection formulation nanoparticles pharmacokinetics Article Catalysis Inorganic Chemistry lcsh:Chemistry Pharmacokinetics medicine Animals Rats Wistar Physical and Theoretical Chemistry Molecular Biology lcsh:QH301-705.5 Spectroscopy Mice Inbred ICR business.industry Organic Chemistry Brain Infarction Middle Cerebral Artery General Medicine Blood flow medicine.disease Hemolysis Computer Science Applications Cilostazol Neuroprotective Agents Blood pressure lcsh:Biology (General) lcsh:QD1-999 Reperfusion Injury Anesthesia Toxicity Administration Intravenous Rabbits business Reperfusion injury medicine.drug |
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 |
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