Hauser H, Gains N, Eibl H J, Müller M, Wehrli E
Biochemistry. 1986 Apr 22;25(8):2126-34. doi: 10.1021/bi00356a042.
The swelling properties of lipid mixtures consisting of phosphatidylcholine and a charged single-chain detergent have been studied. The work presented here is confined to lipid mixtures forming smectic lamellar phases in H2O. These mixtures exhibit continuous swelling with increasing water content, provided the surface charge density exceeds a threshold value of about 1-2 microC/cm2. In excess H2O, such mixtures undergo spontaneous vesiculation: unilamellar vesicles form spontaneously when excess H2O or salt solutions of moderate ionic strength (I less than 0.2) are added to the dried film of such lipid mixtures. The resulting dispersion of unilamellar vesicles is usually polydisperse. Its average size depends on the detergent/phospholipid mole ratio, decreasing with increasing detergent content. It is shown that in the phase diagram of three-component systems consisting of phosphatidylcholine, a charged single-chain detergent, and excess H2O there is a compositional range, though narrow, within which the small unilamellar vesicle (diameter less than 100 nm) is the thermodynamically most stable structure. This behavior is characteristic of charged, single-chain detergents of 14 and more C atoms. Many pharmacologically active compounds are amphiphilic and surface-active, and as such, they will orient at phospholipid-water interfaces, imparting a net surface charge to neutral lipid surfaces. It is shown that such drugs exhibit detergent-like action. Mixed films of phosphatidylcholine and a pharmacologically active compound behave similarly to phosphatidylcholine-detergent mixtures: they undergo spontaneous vesiculation when excess H2O or salt solutions of moderate ionic strength are added. In this case, the drug itself induces vesiculation; possible pharmacological implications of this finding are discussed.
对由磷脂酰胆碱和带电荷的单链去污剂组成的脂质混合物的膨胀特性进行了研究。本文所呈现的工作局限于在水中形成近晶层状相的脂质混合物。只要表面电荷密度超过约1 - 2微库仑/平方厘米的阈值，这些混合物会随着含水量增加而持续膨胀。在过量的水中，此类混合物会发生自发囊泡化：当向这种脂质混合物的干燥膜中加入过量的水或中等离子强度（I小于0.2）的盐溶液时，会自发形成单层囊泡。所得到的单层囊泡分散体通常是多分散的。其平均尺寸取决于去污剂/磷脂的摩尔比，随着去污剂含量增加而减小。结果表明，在由磷脂酰胆碱、带电荷的单链去污剂和过量水组成的三元体系相图中，存在一个组成范围，尽管较窄，但在该范围内小单层囊泡（直径小于100纳米）是热力学上最稳定的结构。这种行为是具有14个及以上碳原子的带电荷单链去污剂的特征。许多药理活性化合物具有两亲性和表面活性，因此，它们会在磷脂 - 水界面定向排列，给中性脂质表面赋予净表面电荷。结果表明，此类药物表现出类似去污剂的作用。磷脂酰胆碱和药理活性化合物的混合膜表现得与磷脂酰胆碱 - 去污剂混合物类似：当加入过量水或中等离子强度的盐溶液时，它们会发生自发囊泡化。在这种情况下，药物本身诱导囊泡化；讨论了这一发现可能的药理学意义。
