Kinetics of Membrane Binding and Mobility of Drugs by Multinuclear Dynamic NMR <i>in Situ</i>

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  • Okamura Emiko
    Faculty of Pharmaceutical Sciences, Himeji Dokkyo University

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  • Kinetics of Membrane Binding and Mobility of Drugs by Multinuclear Dynamic NMR in Situ

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Abstract

Great attention has been paid to molecular dynamics of drug deliveries to lipid bilayer membranes as a primary stage of bioactivities in the cell. Lipid bilayer membranes are dynamic structures where molecules are moving and fluctuating under physiological conditions. Thus the mechanisms of drug deliveries are considered to be relevant to such dynamics in soft, fluid membrane interface. To gain insight into molecular motions and fluctuations in membranes, methods are critical factors to be developed. In this review, a noninvasive strategy to monitor dynamic properties of drugs and lipid membranes is introduced. By applying multinuclear high-resolution solution NMR in combination with the pulsed-field-gradient (PFG) technique, dynamic aspects of drug deliveries have been quantified without undesirable perturbation of the system. Special focus is on how much and how fast drugs are bound to the membrane, and how fast drugs are moving within the membrane in situ by using lipid bilayer vesicles as model cell membranes. An anticancer 5-fluorouracil, a fluorinated derivative of an endocrine disruptor, bisphenol A, a neuropeptide enkephalin, and an anesthetic sevoflurane are compared as a model drug. The effect of cholesterol on deliveries is also discussed in relation to the dynamics in membranes.

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