Bordi F, Cametti C, Motta A, Diociaiuti M, Molinari A
Dipartimento di Medicina Interna, Universita' di Roma Tor Vergata, Rome, Italy.
Bioelectrochem Bioenerg. 1999 Oct;49(1):51-6. doi: 10.1016/s0302-4598(99)00063-x.
The present note describes the use of surface pressure measurements (Langmuir monolayer technique) for the analysis of interactions of two different anthracyclines (adriamycin and daunorubicin) with a non-ionic, zwitterionic phospholipid monolayer, at the air-water interface. Because the surface membrane of the cell is the first barrier encountered by the anthracyclines in the treatment of cancer, drug-membrane interactions studied in model (monolayers or bilayers) and natural systems play an important role in the understanding of the bioactivity properties of these molecules. We report here the rate constants of the adsorption process of adriamycin and daunorubicin in the presence of a zwitterionic phospholipid monolayer at the air-water interface. Because interactions with the lipid monolayer strongly depend on the molecular packing of the lipid, we investigated this process at a relatively low surface pressure (7 mN/m), the interactions being favoured by the gaseous and liquid expanded structure of the lipid monolayer. The apparent molecular area of these molecules during the insertion into the lipid film and their interactions with the phospholipid polar head groups was evaluated and the estimated percentage of anthracyclines at the interface after adsorption into the lipid monolayer is briefly discussed. The rate constants for the adsorption and desorption process at the water-monolayer interface have been calculated on the basis of a single-exponential model. The observed difference of these parameters for daunorubicin and adriamycin suggests a different interaction of these anthracyclines during the adsorption to and/or penetration across the phospholipid monolayer.
本笔记描述了利用表面压力测量（朗缪尔单层技术）分析两种不同蒽环类药物（阿霉素和柔红霉素）与一种非离子两性离子磷脂单层在空气-水界面的相互作用。由于细胞膜表面是蒽环类药物在癌症治疗中遇到的第一道屏障，在模型（单层或双层）和天然系统中研究的药物-膜相互作用对于理解这些分子的生物活性特性起着重要作用。我们在此报告阿霉素和柔红霉素在空气-水界面存在两性离子磷脂单层时的吸附过程速率常数。由于与脂质单层的相互作用强烈依赖于脂质的分子堆积，我们在相对较低的表面压力（7 mN/m）下研究了这一过程，脂质单层的气态和液体膨胀结构有利于这种相互作用。评估了这些分子插入脂质膜过程中的表观分子面积及其与磷脂极性头部基团的相互作用，并简要讨论了吸附到脂质单层后界面处蒽环类药物的估计百分比。基于单指数模型计算了水-单层界面处吸附和解吸过程的速率常数。柔红霉素和阿霉素这些参数的观察差异表明，这些蒽环类药物在吸附到磷脂单层和/或穿过磷脂单层的过程中存在不同的相互作用。
