Determination of liposome permeability of ionizable carbamates of zidovudine by steady state fluorescence spectroscopy.
In the present paper the relative permeabilities of AZT-Pyp and AZT-Ethy across a phospholipid bilayer were estimated by the means of fluorescence spectroscopy. The center of spectral mass of both non-encapsulated AZT-derivatives (AZT-der) emission spectra increased as a function of the illumination time inside the spectrofluorimeter cell. This phenomenon was even more evident when drugs were incubated under an UV mercury lamp, suggesting its photolytic origin. AZT-der were protected from photolysis inside liposomes and decomposed upon irradiation when they were free in the aqueous phase. The time-dependent decrease in the fluorescence intensity at a constant wavelength was fitted to a two-exponential equation and the values of rate constants for permeability and photolysis were calculated. It was concluded that AZT-Pyp but not AZT-Ethy diffused across the bilayer. This behavior correlated with the molecular volumes of AZT-Pyp (379.6A(3)) and AZT-Ethy (450.5A(3)), determined from the minimum energy conformations but not with previously reported logP values. These results reinforce the concept that not only lipophilicity but also membrane structure and AZT-der molecular size had a critical influence in passive diffusion across bilayers and may help in future refinements of other AZT-der molecular design.
Raviolo
Mónica A
MA
Departamento de Farmacia, Facultad de Ciencias Químicas, Argentina.
Sanchez
Julieta M
JM
Briñón
Margarita C
MC
Perillo
María A
MA
D002219:Carbamates / Q000737:chemistry*; D003902:Detergents / Q000737:chemistry; D016503:Drug Delivery Systems; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes; D008968:Molecular Conformation; D010539:Permeability; D010782:Photolysis; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D015215:Zidovudine / Q000031:analogs & derivatives / Q000737:chemistry*
D002219:Carbamates; D003902:Detergents; D008051:Lipid Bilayers; D008081:Liposomes; D015215:Zidovudine