Borissevitch G P, Tabak M, Oliveira O N
Instituto de Química de São Carlos, Brazil.
Biochim Biophys Acta. 1996 Jan 12;1278(1):12-8. doi: 10.1016/0005-2736(95)00208-1.
Dipyridamole (DIP), a well known coronary vasodilator and coactivator of anti-tumor activity of a number of drugs, forms stable Langmuir monolayers with the zwitterionic lipid dipalmitoylphosphatidylcholine (DPPC) and the negatively charged dipalmitoylphosphatidylglycerol (DPPG) at an air/aqueous solution interface. The drug binds to the lipid molecules and change their packing density in the monolayer in the process of compression, the effect depending on the drug location in the monolayer, protonation of the drug and also on the charge state of the lipid. The incorporation of dipyridamole (DIP) into neutral DPPC monolayers causes them to be more expanded at low DIP concentrations but more condensed at high concentrations, resembling the effect of cholesterol. Maximum expansion occurs for a DIP concentration of 2 mol%. For slightly charged DPPG monolayers spread on ultra pure water, the monolayers become increasingly more expanded with increasing DIP concentrations. For the negatively charged DPPG monolayers spread on buffer solutions, the incorporation of DIP has similar effects to that observed for DPPC monolayers. This is probably due to the interaction between the charged DPPG molecules and the protonated DIP molecules. Also, introduction of protonated DIP brings an increase in surface potential of DPPG monolayers because the negative contribution from the double layer is decreased. The results indicated that DIP molecules are located deeper in the hydrophobic region of DPPC monolayers, whereas in DPPG ones they appear to be located very close to the polar head region. Due to the electrostatic interaction of protonated DIP with the charges on the polar heads of lipids it is inclined with respect to the plane of the monolayer.
双嘧达莫（DIP）是一种著名的冠状动脉血管扩张剂，也是多种药物抗肿瘤活性的共激活剂，它在空气/水溶液界面与两性离子脂质二棕榈酰磷脂酰胆碱（DPPC）和带负电荷的二棕榈酰磷脂酰甘油（DPPG）形成稳定的朗缪尔单层膜。在压缩过程中，该药物与脂质分子结合并改变它们在单层膜中的堆积密度，这种效应取决于药物在单层膜中的位置、药物的质子化以及脂质的电荷状态。将双嘧达莫（DIP）掺入中性DPPC单层膜中，在低DIP浓度下会使其更膨胀，而在高浓度下则更凝聚，类似于胆固醇的作用。当DIP浓度为2 mol%时，膨胀达到最大值。对于铺展在超纯水上的略带电荷的DPPG单层膜，随着DIP浓度的增加，单层膜变得越来越膨胀。对于铺展在缓冲溶液上的带负电荷的DPPG单层膜，掺入DIP产生的效果与在DPPC单层膜中观察到的相似。这可能是由于带电荷的DPPG分子与质子化的DIP分子之间的相互作用。此外，引入质子化的DIP会使DPPG单层膜的表面电位增加，因为双层的负贡献减少了。结果表明，DIP分子位于DPPC单层膜疏水区域的更深位置，而在DPPG单层膜中它们似乎非常靠近极性头部区域。由于质子化的DIP与脂质极性头部的电荷之间的静电相互作用，它相对于单层膜平面倾斜。
