Molecular interactions between lipid and paclitaxel (Taxol/sup (R)/) within cell membrane simulated by the lipid monolayer at the air-water interface

Abstract

Paclitaxel (Taxol(R)) is a novel antineoplastic drug with a high potency against advanced ovarian and breast cancer. However, clinical application has been hampered by the poor aqueous solubility of taxol, which necessitates administration of the drug in excipients (Cremophor EL and ethanol). These adjvants cause a variety of side effects, including anaphylactoid hypersensitivity reactions. Recently, Taxol has been formulated in better-tolerable drug carriers such as liposomes. In this paper we use the lipid monolayer at the air-water interface to simulate the bilayer vesicles and the cell membrane in characterization of the molecular interaction between Taxol and phospholipid (DPPC) within the membrane. It was found that at 25/spl deg/C the penetration of Taxol into DPPC membrane alters the surface pressure dramatically, especially in low molar ratio of Taxol:DPPC (<1:2). Penetration kinetics studies showed that Taxol molecules have intensive interaction with DPPC monolayer. The critical surface pressure for Taxol molecules to partition into the DPPC membrane is around 31 mN/m.