THE ACCUMULATION OF DRUGS WITHIN LARGE UNILAMELLAR VESICLES EXHIBITING A PROTON GRADIENT - A SURVEY
THE ACCUMULATION OF DRUGS WITHIN LARGE UNILAMELLAR VESICLES EXHIBITING A PROTON GRADIENT - A SURVEY
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DOI：
10.1016/0009-3084(90)90131-a
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发表时间：
1990-03-01
影响因子：
3.4
通讯作者：
CULLIS, PR
中科院分区：
文献类型：
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作者：
MADDEN, TD;HARRIGAN, PR;CULLIS, PR
我们之前已经证明，跨膜质子梯度可用于有效积累生物胺 [M.B.巴利等人。 （1988）化学。物理。脂质 47, 97 - 107] 和阿霉素 [L.D.梅耶尔，M.B. Bally 和 P.R. Cullis (1986) Biochim。生物物理学。 Acta 857, 123 - 126] 在脂质体内达到高浓度。为了确定这种装载程序的普遍性，检查了各种不同类别的代表性药物（抗肿瘤药、局部麻醉药、抗组胺药等）的响应质子梯度重新分布的能力。虽然所检查的大多数药物均为弱碱，但都是由表现出 pH 梯度（内部酸性）的大单层囊泡积累的，但不同药物之间的吸收程度差异很大。这些差异是在可能影响药物积累的各种因素的背景下讨论的，包括其膜/水分配系数及其在囊泡内介质中的溶解度。
We have shown previously that transmembrane proton gradients can be used to efficiently accumulate biogenic amines [M.B. Bally et al. (1988) Chem. Phys. Lipids 47, 97 - 107] and doxorubicin [L.D. Mayer, M.B. Bally and P.R. Cullis (1986) Biochim. Biophys. Acta 857, 123 - 126] to high concentrations within liposomes. To determine the generality of this loading procedure, representative drugs from a variety of different classes (antineoplastics, local anaesthetics, antihistamines, etc.) were examined as to their ability to redistribute in response to a proton gradient. While the majority of drugs examined, all of which are weak bases, were accumulated by large unilamellar vesicles exhibiting a pH gradient (interior acid) the extent of uptake varied considerably between different pharmaceuticals. These differences are discussed in the context of various factors which will likely influence drug accumulation including its membrane/water partition coefficient and its solubility in the intravesicular medium.