Molecular interactions between a lipid and an antineoplastic drug paclitaxel (taxol) within the lipid monolayer at the air/water interface

Abstract

The lipid monolayer at the air/water interface was used to simulate large bilayer vesicles and the cell membrane in characterization of molecular interactions between the phospholipid and an antineoplastic drug paclitaxel (taxol), which is one of the best anticancer drugs found from nature in the past decades. The mixed lipid/paclitaxel monolayers of various molar ratios were formed at the air/water interface in a Langmuir trough, and the surface pressure versus molecular area isotherms were measured upon compression of the monolayers. It was found from the analysis of membrane mechanics and thermodynamics that the two components were miscible and formed a nonideally mixed monolayer at the air/water interface. It was shown that introduction of paclitaxel into the dipalmitoyl phosphocholine (DPPC) monolayer caused instability of the monolayer, which was due to the molecular interactions between the two components. Similar results were also obtained by Fourier tranform infrared (FTIR) spectroscopy and atomic force microscopy (AFM) investigation of the mixed monolayers, which were deposited onto a solid surface at a desired surface pressure. The FTIR analysis showed that introduction of paclitaxel into the lipid monolayer increases the mobility of the acyl chains of the lipid, resulting a fluidizing effect on the monolayer. Paclitaxel increases the population of trans conformers at low surface pressures and the proportion of gauche conformers at high surface pressures. The AFM analysis demonstrated that introduction of paclitaxel into the lipid monolayer reduces the extent of liquid-condensed phases and causes a reorganization of microdomains of the monolayers.