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  • Title: Interaction of the anticancer agent Taxol (paclitaxel) with phospholipid bilayers.
    Author: Bernsdorff C, Reszka R, Winter R.
    Journal: J Biomed Mater Res; 1999 Aug; 46(2):141-9. PubMed ID: 10379991.
    Abstract:
    Taxol (paclitaxel), a promising agent for use in ovarian and breast cancer, was incorporated into lipid vesicles (liposomes) composed of different saturated and unsaturated phosphatidylcholines, as well as saturated phosphatidylcholines mixed with the anionic phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphatidylserine (DMPS) at different molar ratios, to yield information about Taxol-liposome interactions. For the physicochemical characterization of the thermodynamic, structural, and dynamic properties of these mixtures, differential scanning calorimetry (DSC), steady-state fluorescence depolarization, and Fourier transform IR spectroscopy was used. Time-dependent DSC measurements on 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC)/Taxol mixtures of different concentrations were performed to yield information on the long-term stability of Taxol-liposome complexes. Partitioning of Taxol into saturated lipid bilayers results in changes of membrane physical properties, such as phase transition temperatures and lipid order parameter, that are different from those observed for unsaturated and charged phospholipid bilayers. Taxol incorporated into saturated phospholipids changes their thermotropic phase behavior: it reduces the lipid order parameter (i.e., has a "fluidizing" effect) in the gel phase of the lipid bilayers. On the contrary, partitioning of Taxol into unsaturated fluid phospholipid bilayers has a slight "rigidization" effect. The saturated lipid bilayer systems DPPC and 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine/DMPS have been identified with the highest incorporation efficiency for Taxol and are thus candidates for drug vehicles that can improve the therapeutic efficacy of Taxol.
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