Localization of drug molecules

X-ray diffraction [72], often in combination with DSC or NMR, is another useful tool for the study of drug-membrane interactions. It is especially useful to obtain information on the localization of drag molecules and on the conformational (phase) changes of membranes. The method is based on comparing the electron density profile of membranes to which drug has or has not been added. If partially hydrated probes are used, coherent Bragg-like scattering is obtained at reasonable resolution. 

Jelinek and co-workers demonstrated that the changes in fluorescence of PDA can be used to detect the interactions of drug molecules with the membranes of live cells. Diacetylene patches containing 10,12-tricosadiynoic acid were transferred from diacetylene vesicles to the membranes of leukemia cells and were polymerized with UV radiation. This fusion efficiency was found to depend on the lipid composition of the liposomes and the presence of cholesterol on the plasma membrane. The interactions of these cells with lidocaine (a local anesthetic), polymixin-B (an antibiotic), and oleic acid were studied by confocal fluorescence microscopy. The PDA patch on the live cells showed bright red fluorescence when the cell membranes were perturbed. The blue to red color change in the presence of oleic acid was apparent when the cells were sedimented by centrifugation. 

The ending caine stems from cocaine, the first clinically employed local anaesthetic. Procaine and tetracaine are ester-linked substances, the others are amides. Amide bonded local anaesthetics usually contain two i s in their name, ester-bonded only one. In the structure drawings, the lipophilic portion of the molecule is depicted at the left, the amine at the right. The asterisk marks the chiral centre of the stereoisomeric drugs. Lipid solubility is given as the logarithm of the water octanol partition coefficient, log(P). 

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