Investigations on the role of ionic liquid on the physicochemical characteristics and toxicological consequences of liposomes

Abstract

Effect of 1-butyl-3-methylimidazolium chloride ionic liquid ([bmim]Cl, IL) on the monolayer/bilayer of either soy-phosphatidylcholine (SPC) or hydrogenated soy-phosphatidylcholine (HSPC), in combination with 30 ​mol% cholesterol (Chol), were investigated. Impact of IL on monolayers were explored by measuring the surface pressure (π)-area (A) isotherm with a Langmuir-surface balance. Lift-off area (A₀) of the monomolecular films gradually increased [A_0(HSPC+IL) ​> ​A_0(SPC+IL)], collapse pressures (π_c) decreased and passed through minima [π_c(HSPC+IL) ​> ​π_c(SPC+IL)] with increasing IL concentration ([IL]). Minimum molecular area (A_min) increased monotonously and compression moduli (C_s⁻¹) followed the sequence (HSPC+IL) ​> ​(SPC+IL) at a particular π with respect to [IL]. Dynamic light scattering studies were carried out to determine the hydrodynamic diameter (d_h), zeta potential (Z.P.) and polydispersity index (PDI) values while fluorescence anisotropy studies, using 7-hydroxycoumarin and 1,6-diphenyl-1,3,5-hexatriene, could reveal the micro-viscosity of liposomes. Increased size and rigidity, induced by IL, suggest the formation of leak-proof, condensed liposomes. Disruption of vesicles induced by IL were observed from transmission electron microscopic (TEM) studies. IL induced disintegration of liposome and kinetics of subsequent formation of adsorbed monolayer were accomplished by surface pressure-time isotherms. IL-induced liposomes were substantially less toxic as revealed by MTT assay. These liposomes are considered to be safely used as effective and controlled drug delivery systems.