Encapsulation of an antivasospastic drug, fasudil, into liposomes, and in vitro stability of the fasudil-loaded liposomes
Encapsulation of an antivasospastic drug, fasudil, into liposomes, and in vitro stability of the fasudil-loaded liposomes
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DOI：
10.1016/s0378-5173(01)00896-1
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发表时间：
2002-01-31
影响因子：
5.8
通讯作者：
Kiwada, H
中科院分区：
文献类型：
--
作者：
Ishida, T;Takanashi, Y;Kiwada, H
本工作的目的是开发法舒地尔脂质体。一种抗血管痉挛药作为将包封的药物递送到脑中以及表征脂质体制剂的体外稳定性的可能手段。建立了HI或硫酸铵的跨膜电化学梯度，并检查了它们对法舒地尔摄入预先形成的氢化大豆磷脂酰胆碱/胆固醇（HSPC/CHOL）脂质体的影响。法舒地尔成功地加载到预先形成的脂质体中，以响应硫酸根离子（SO 42）和。部份地是H+。接近100%的包封水平可以达到高达0.364（mol/mol）的药物与脂质比。通过在4 ℃下在4-（2-羟乙基）-1-哌嗪乙磺酸（HEPES）缓冲液（pH 7.4）中储存和在37 ℃下在人脑脊液（CSF）中孵育，进行法舒地尔负载脂质体的稳定性研究。在研究期间，制剂在药物保留和尺寸变化方面保持稳定。泄漏研究清楚地显示了法舒地尔负载脂质体在人CSF中的缓释特性。我们最近报道，鞘内给予脂质体法舒地尔显著减少缺血，在大鼠模型中没有明显的不良作用[Neurol. Med. Chir. 41（21001）109]。综上所述，法舒地尔有效地包封到预先形成的脂质体中。其在4 ℃下的长期稳定性和在CSF中的持续释放特性表明法舒地尔负载脂质体可作为进一步临床评价的潜在候选物。(C)2002 Elsevier Science B. V.保留所有权利。
The objectives of this work were to develop a liposomal fasudil. an antivasospastic drug. as a possible means to deliver the encapsulated drug to the brain, and to characterize the stability of the liposomal formulation in vitro. Transmembrane electrochemical gradients of H I or ammonium sulfate were created, and their effect on the uptake of fasudil into preformed hydrogenated soy phosphatidylcholine/cholesterol (HSPC/CHOL) liposomes were examined. Fasudil was successfully loaded into preformed liposomes in response to sulfate ion (SO42) and. in part. by H+. Encapsulation levels approaching 100% could be achieved up to a drug to lipid ratio of 0.364 (mol/mol). A stability study of the fasudil-loaded liposomes was performed by storage at 4 degreesC in 4-(2-hydroxyethyl)-1-piper-azineethanesulphonic acid (HEPES)-buffer (pH 7.4) and by incubation in human cerebrospinal fluid (CSF) at 37 degreesC. The formulations were stable with respect to drug retention as well as size alteration, for the period Studied. A leakage study clearly showed the sustained release properties of the Fasudil-loaded liposomes in human CSF. We recently reported that the intrathecal administration of liposomal fasudil significantly decreased ischemia, with no obvious adverse effect in a rat model [Neurol. Med. Chir. 41 (21001) 109]. Taken together, efficient encapsulation of fasudil into preformed liposomes. their long-term stability at 4 degreesC and the sustained release characteristics in CSF indicate that fasudil-loaded liposomes could be potential candidates for further clinical evaluation. (C) 2002 Elsevier Science B.V. All rights reserved.