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  • Title: Insertion and partition of sodium taurocholate into egg phosphatidylcholine vesicles.
    Author: Andrieux K, Forte L, Lesieur S, Paternostre M, Ollivon M, Grabielle-Madelmont C.
    Journal: Pharm Res; 2004 Aug; 21(8):1505-16. PubMed ID: 15359588.
    Abstract:
    PURPOSE: To get a continuous description of the insertion and partition processes of sodium taurocholate (TC) into the lipid bilayers of vesicles that can serve as a model for understanding the mechanism of destabilization by the bile salts of liposomes used as drug carriers for oral administration. METHODS: The progressive solubilization of egg phosphatidylcholine vesicles during TC addition at controlled rates was followed by continuous turbidity (OD) and resonance energy transfer (RET) between two fluorescent probes. The influence of the lipid and TC concentrations as well as the rate of TC addition on the processes were examined. RESULTS: Continuous turbidity recordings allowed following of the size and composition evolutions of the mixed TC/lipid aggregates formed at different steps of the vesicle-micelle transition. The solubilization mechanism is governed by complex kinetics that depend on the surfactant concentration and its addition rate. A two-step process characterizes the evolution of the vesicular state: interaction of TC molecules with the external monolayer of the vesicles first occurs. The homogeneous distribution of TC within the lipid matrix after its insertion is a very slow process. A micellar structural reorganization is observed when TC is added rapidly. CONCLUSIONS: This work provides detailed information on the slow insertion and diffusion kinetics of TC in liposomal bilayers by using a dynamic study which mimics physiological phenomena of digestion.
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