Nagai Noriaki, Yoshioka Chiaki, Ito Yoshimasa, Funakami Yoshinori, Nishikawa Hiroyuki, Kawabata Atsufumi
Faculty of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan.
Int J Mol Sci. 2015 Dec 9;16(12):29329-44. doi: 10.3390/ijms161226166.
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.
据报道，西洛他唑（CLZ）可抑制缺血区域微血管的破坏。在本研究中，我们使用0.5%甲基纤维素、0.2%十二烷基磺酸钠及研磨法设计了含CLZ纳米颗粒的新型注射制剂（CLZ纳米分散体；粒径81±59nm，平均值±标准差），并在大脑缺血/再灌注损伤模型（大脑中动脉闭塞/再灌注小鼠）中研究了其毒性和效用。CLZ纳米分散体注射剂的药代动力学与用2-羟丙基-β-环糊精制备的CLZ溶液相似，且CLZ纳米分散体未观察到细胞损伤模型兔红细胞溶血率的变化。此外，静脉注射0.6mg/kg CLZ纳米分散体不影响血压和血流，且0.6mg/kg CLZ纳米分散体可改善大脑中动脉闭塞/再灌注小鼠的神经功能缺损和缺血性中风。CLZ纳米分散体有可能为缺血性中风患者提供有效的治疗，且含药物纳米颗粒的亲脂性药物注射制剂可扩大其治疗用途。
