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DSC and EPR investigations on effects of cholesterol component on molecular interactions between paclitaxel and phospholipid within lipid bilayer membrane

Zhao, Lingyun and Feng, Si-Shen and Kocherginsky, Nikolai and Kostetski, Iouri (2007) DSC and EPR investigations on effects of cholesterol component on molecular interactions between paclitaxel and phospholipid within lipid bilayer membrane. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 338 (1-2). pp. 258-266.

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Official URL: http://www.sciencedirect.com/science?_ob=ArticleUR...

Abstract

Differential scanning calorimetry (DSC) and electron paramagnetic resonance spectroscopy (EPR) were applied to investigate effects of cholesterol component on molecular interactions between paclitaxel, which is one of the best antineoplastic agents found from nature, and dipalmitoylphosphatidylcholine (DPPC) within lipid bilayer vesicles (liposomes), which could also be used as a model cell membrane. DSC analysis showed that incorporation of paclitaxel into the DPPC bilayer causes a reduction in the cooperativity of bilayer phase transition, leading to a looser and more flexible bilayer structure. Including cholesterol component in the DPPC/paclitaxel mixed bilayer can facilitate the molecular interaction between paclitaxel and lipid and make the tertiary system more stable. EPR analysis demonstrated that both of paclitaxel and cholesterol have fluidization effect on the DPPC bilayer membranes although cholesterol has more significant effect than paclitaxel does. The reduction kinetics of nitroxides by ascorbic acid showed that paclitaxel can inhibit the reaction by blocking the diffusion of either the ascorbic acid or nitroxide molecules since the reaction is tested to be a first order one. Cholesterol can remarkably increase the reduction reaction speed. This research may provide useful information for optimizing liposomal formulation of the drug as well as for understanding the pharmacology of paclitaxel. (c) 2007 Elsevier B.V. All rights reserved.

Item Type:Article
Uncontrolled Keywords:anticancer drugs; differential scanning calorimetry (DSC); electron paramagnetic resonance spectroscopy (EPR); liposomes; nanomedicine; Taxol((R))
Subjects:Biomedical Science > Nanotechnology for human health
Biomedical Science > Nanomedicine
ID Code:2718
Deposited By:Farnush Anwar
Deposited On:09 Jan 2009 10:55
Last Modified:09 Jan 2009 10:55

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