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Title: Investigation of Molecular Interactions between Paclitaxel and DPPC by Langmuir Film Balance and Differential Scanning Calorimetry
Authors: Zhao, L. 
Feng, S.-S. 
Go, M.L. 
Keywords: Cancer chemotherapy
Issue Date: Jan-2004
Citation: Zhao, L., Feng, S.-S., Go, M.L. (2004-01). Investigation of Molecular Interactions between Paclitaxel and DPPC by Langmuir Film Balance and Differential Scanning Calorimetry. Journal of Pharmaceutical Sciences 93 (1) : 86-98. ScholarBank@NUS Repository.
Abstract: Molecular interactions between paclitaxel and dipalmitoylphosphatidyl choline (DPPC) were investigated by Langmuir film balance and differential scanning calorimetry (DSC). Both the lipid monolayer at the air-water interface and that in the lipid bilayer vesicles (liposomes) were employed as model cell membranes. Thermodynamic and kinetic analyses of the DPPC/pacltaxel monolayer system and the paclitaxel penetration into the DPPC monolayer showed that DPPC and paclitaxel can form a nonideal miscible system in the lipid monolayer over a wide range of the DPPC/paclitaxel molar ratios. Paclitaxel exerts an area-condensing effect on the DPPC monolayer at small molecular areas and an area-expanding effect at large molecular areas on the π-A behavior of the DPPC monolayer, which can be explained by the intermolecular forces and geometric accommodation between paclitaxel and DPPC. Based on a calculation of the excess free energy of the mixed monolayer system, the most stable state of the system occurs at the monolayer composition of 5% paclitaxel. Penetration kinetics showed that the paclitaxel penetration into the DPPC monolayer increases with increasing the drug concentration in the subphase, but there is a limit of ∼500 ng/mL. Any further increase in paclitaxel concentration had no additional significant effects on the drug penetration. Differential scanning calorimetry showed that paclitaxel caused broadening of the main phase transition. There was no significant change in the peak melting temperature of the DPPC bilayers, which demonstrated that paclitaxel was localized in the outer hydrophobic cooperative zone of the bilayer. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association.
Source Title: Journal of Pharmaceutical Sciences
ISSN: 00223549
DOI: 10.1002/jps.10523
Appears in Collections:Staff Publications

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