title: Paclitaxel partitioning into lipid bilayers.
abstract: Paclitaxel (taxol) is diterpenoid anticancer drug with a new mechanism of cytostatic action. It is under investigation in clinical trials for treatment of various types of human cancer. A major difficulty in developing paclitaxel as a chemotherapeutic agent in its poor water solubility. In order to improve the bioavailability of paclitaxel, novel vehicle systems such as mixed micelles or liposome-based formulations are being developed. In this study we determined the partition coefficient of paclitaxel partitioning into small unilamellar lipid vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine using two different methods, namely high-sensitivity titration calorimetry and fluorescence spectrometry. We measured a partition coefficient of Kp approximately equal to 9,500 M-1, a partition enthalpy of Delta H = -25 +/- 3 kcal mol-1 and a free energy of binding of Delta G = -7.9 kcal mol-1. The binding reaction is enthalpy-driven, which can be explained by van der Waals interactions between the hydrophobic drug and the strong temperature dependence of the partition equilibrium. A temperature increase of 10 degrees C reduces the paclitaxel solubility in the lipid phase by a factor of 4.
authors.affiliation: Department of Biophysics, University of Basel, Switzerland.
authors.forename: M R
authors.initials: MR
authors.lastname: Wenk
authors.forename: A
authors.initials: A
authors.lastname: Fahr
authors.forename: R
authors.initials: R
authors.lastname: Reszka
authors.forename: J
authors.initials: J
authors.lastname: Seelig
mesh_terms: D008051:Lipid Bilayers / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry*; D013696:Temperature; D013997:Time Factors
chemical_list: D008051:Lipid Bilayers; D017239:Paclitaxel