title: Interaction of rifampicin and isoniazid with large unilamellar liposomes: spectroscopic location studies.
abstract: The location of isoniazid and rifampicin, two tuberculostatics commonly used for the treatment of Mycobacterium tuberculosis and Mycobacterium avium complex infectious diseases, in bilayers of dimyristoyl-L-alpha-phosphatidylcholine (DMPC) and dimyristoyl-L-a-phosphatidylglycerol (DMPG) have been studied by 1H NMR and fluorimetric methods. Steady-state fluorescence intensity and fluorescence energy transfer studies between rifampicin and a set of functionalized probes [n-(9-anthroyloxy)stearic acids, n=2, 12] reveal that, in both systems, isoniazid is located at the membrane surface whereas rifampicin is deeply buried inside the lipid bilayers. Steady-state fluorescence anisotropy studies performed with the probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and trimethylammonium-diphenylhexa-triene (TMA-DPH), not only corroborate the above results, but also show that no changes in membrane fluidity were detected in either liposome. The 1H NMR results, in DMPC liposomes, confirm the location of rifampicin near the methylene group of the acyl chains of the lipid bilayers.
authors.affiliation: CEQUP/Faculdade de Ciências, Departamento de Qui;mica, Universidade do Porto, R. Campo Alegre 687, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Rodrigues
authors.forename: Paula
authors.initials: P
authors.lastname: Gameiro
authors.forename: M
authors.initials: M
authors.lastname: Prieto
authors.forename: Baltazar
authors.initials: B
authors.lastname: de Castro
mesh_terms: D000904:Antibiotics, Antitubercular / Q000737:chemistry*; D004134:Dimyristoylphosphatidylcholine; D005470:Fluorometry; D057927:Hydrophobic and Hydrophilic Interactions; D007538:Isoniazid / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015335:Molecular Probes; D010715:Phosphatidylglycerols; D012293:Rifampin / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D000904:Antibiotics, Antitubercular; D008051:Lipid Bilayers; D008081:Liposomes; D015335:Molecular Probes; D010715:Phosphatidylglycerols; C002773:dimyristoylphosphatidylglycerol; D004134:Dimyristoylphosphatidylcholine; D007538:Isoniazid; D012293:Rifampin