Role of copper gluconate/triethanolamine in irinotecan encapsulation inside the liposomes
Role of copper gluconate/triethanolamine in irinotecan encapsulation inside the liposomes
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DOI：
10.1016/j.ijpharm.2007.01.004
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发表时间：
2007-06-07
影响因子：
5.8
通讯作者：
Mayer, Lawrence
中科院分区：
文献类型：
--
作者：
Dicko, Awa;Tardi, Paul;Mayer, Lawrence
最近开发了一种将伊立替康包封到含有用三乙醇胺（TEA）缓冲至pH 7.0的葡萄糖酸铜的脂质体中的新方法。在本研究中，研究了这些脂质体中药物包封和保留的机制。光谱分析显示，伊立替康与葡萄糖酸铜/TEA在溶液中相互作用。傅立叶变换红外（FT-IR）光谱表明，当伊立替康和葡萄糖酸铜/TEA溶液以1：1摩尔比混合时，涉及羟基的氢键增强。在存在等摩尔量伊立替康的情况下，葡萄糖酸铜/TEA的圆二色性（CD）信号强度增加。在50 ℃下向含有葡萄糖酸铜/TEA的脂质体中加入伊立替康诱导吸收带从370 nm移动至378 nm，以及440 nm处药物荧光猝灭60%，表明发生伊立替康自缔合。发现伊立替康包封与脂质体中TEA的释放在动力学和化学计量学上相关。结果表明，伊立替康的包封由TEA与葡萄糖酸铜联合介导，导致最终药物复合物保留在脂质体内。提出了伊立替康和TEA之间的中性反向交换负载机制。(c)2007 Elsevier B. V.保留所有权利。
A novel method for encapsulating irinotecan into liposomes containing copper gluconate buffered to pH 7.0 with triethanolamine (TEA) has recently been developed. In the present study, the mechanism dictating drug encapsulation and retention inside those liposomes was investigated. Spectroscopic analyses revealed that irinotecan interacted with copper gluconate/TEA in solution. Fourier transformed infrared (FT-IR) spectroscopy indicated a strengthening of the hydrogen bonds involving the hydroxyl groups when solutions of irinotecan and copper gluconate/TEA are mixed at a 1: 1 molar ratio. The intensity of the circular dichroism (CD) signal of copper gluconate/TEA increased in the presence of equimolar amounts of irinotecan. The addition of irinotecan to liposomes containing copper gluconate/TEA at 50 degrees C induced a shift of the absorption bands from 370 nm to 378 mn as well as a 60% quenching of the drug fluorescence at 440 nm suggesting the occurrence of irinotecan self association. Irinotecan encapsulation was found to be kinetically and stoichiometrically correlated with the release of TEA from the liposomes. The results suggested that the encapsulation of irinotecan was mediated by TEA in association with copper gluconate, leading to a final drug complex that is retained inside the liposomes. A neutral antiport exchange loading mechanism between irinotecan and TEA is proposed. (c) 2007 Elsevier B.V. All rights reserved.