Influence of Substituents in β-Cyclodextrin on the Interaction of Levofloxacin–β-Cyclodextrin Complexes with Liposomal Membrane

The effect of substituents (polar CH2CH(OH)CH3, hydrophobic CH3, and charged $${{\left( {{\text{C}}{{{\text{H}}}_{{\text{2}}}}} \right)}_{{\text{4}}}}{\text{SO}}_{3}^{ - }$$ ) in β-cyclodextrin (CyD ) on the formation of defects in a liposomal bilayer, as well as on the interaction with an fluoroquinolone-type antibacterial drug, levofloxacin (LV), has been studied. Equilibrium dialysis has been employed to show that 2-hydroxypropyl-β-cyclodextrin induces the formation of greatest defects in the bilayer. CyDs bearing hydroxypropyl (HP-CyD) and methyl (М-CyD) substituents enhance the interaction of LV with the lipid bilayer, as is evident from circular dichroism spectroscopy data. All studied LV complexes with CyD derivatives are adsorbed on the bilayer due to electrostatic interactions between phosphate groups of lipids and positively charged nitrogen atoms in LV heterocycles. The enhancement in the adsorption of LV complexed with CyD derivatives on the bilayer has also been analyzed by measuring the ζ-potential of liposomes. As the content of CyD–LV complexes in a dispersion of liposomes is increased, their ζ-potential varies in a different ways because of the differences in the dissociation constants of the complexes. In spite of the fact that HP-CyD has a stronger effect on the state of the liposomal membrane than other CyD derivatives due to the large number of hydroxyl groups, the negative values of the ζ-potential of the liposomes in the presence of HP-CyD–LV complex are only slightly lower than those in the presence of free LV because of the highest dissociation constant of this complex. At the same time, M-CyD–LV and SB-CyD−LV complexes neutralize liposome charge much more efficiently.