Abstract

The interaction between 2-hydroxypropyl β-cyclodextrin (HPCD) and a liposomal bilayer has been studied. The main binding sites of HPCD on the surface of neutral liposomes based on dipalmitoylphosphatidylcholine (DPPC) are the phosphate groups of lipids. The complex formation with HPСD leads to the stabilization of the gel state of monocomponent liposomes. The inclusion of the anionic component, cardiolipin (CL, 20%), in the bilayer changes the nature of the liposome-HPCD interaction. The observed lipid disorder disturbs membrane integrity, which is revealed in the release of the included dye (phenolphthalein). The effect of HPCD on the process and parameters of the phase transition of anionic liposomes has been studied using thermograms, which show the change in the position of the absorption bands of lipid acyl chains in the FTIR spectrum of liposomes. A stratification of DPPC/CL (80/20%) bilayer into two microphases with different cardiolipin content has been detected. HPCD causes the more pronounced stratification in the bilayer, i.e., membrane destabilization near the melting point of CL-rich microphase and, vice versa, a decrease in the lipid mobility in regions with a low CL content. We have studied the effect of HPCD on the interaction of an antibacterial drug, levofloxacin (LV), with the lipid bilayer. It has been found that the complexation of the drug molecules with HPCD leads to an increase in the efficiency of drug adsorption on the surface of the bilayer. This may facilitate the transport of the drug through the bilayer due to the formation of defects in the membrane. LV in the complex with HPCD shows a high antibacterial efficiency in vitro against E. coli, which is not lower as compared with free LV.

中文翻译：

---

通过与2-羟丙基β-环糊精相互作用调节脂质膜的性质：分子细节

摘要

研究了2-羟丙基β-环糊精（HPCD）和脂质体双层之间的相互作用。基于二棕榈酰磷脂酰胆碱（DPPC）的中性脂质体表面上HPCD的主要结合位点是脂质的磷酸基团。与HPСD形成的复合物导致单组分脂质体的凝胶状态稳定。双层中包含阴离子成分心磷脂（CL，20％）会改变脂质体-HPCD相互作用的性质。观察到的脂质紊乱扰乱了膜的完整性，这在所含染料（酚酞）的释放中得以体现。已使用热谱图研究了HPCD对阴离子脂质体相变过程和参数的影响，这些图显示了脂质体FTIR光谱中脂质酰基链吸收带位置的变化。已检测到将DPPC / CL（80/20％）双层分层为两个心磷脂含量不同的微相。HPCD在双层中引起更明显的分层，即在富含CL的微相的熔点附近发生膜不稳定，反之亦然，在CL含量低的区域中脂质迁移率降低。我们已经研究了HPCD对抗菌药物左氧氟沙星（LV）与脂质双层相互作用的影响。已经发现，药物分子与HPCD的络合导致双层表面上药物吸附的效率增加。由于在膜中形成缺陷，这可以促进药物通过双层的运输。大肠杆菌，与游离LV相比并不低。