Determination of liposome permeability of ionizable carbamates of zidovudine by steady state fluorescence spectroscopy

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2008-02, Vol.61 (2), p.188-198
• Main Authors: Raviolo, Mónica A., Sanchez, Julieta M., Briñón, Margarita C., Perillo, María A.
• Format: Article
• Language: English
• Subjects: AZT-carbamates; Carbamates - chemistry; Detergents - chemistry; Drug Delivery Systems; Fluorescence; Hydrophobic and Hydrophilic Interactions; Kinetics; Lipid Bilayers - chemistry; Liposomes; Molecular Conformation; Permeability; Phospholipids bilayer; Photolysis; Spectrometry, Fluorescence; Time Factors; Zidovudine - analogs & derivatives; Zidovudine - chemistry
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2007.08.004

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 (379.6 Å 3) and AZT-Ethy (450.5 Å 3), determined from the minimum energy conformations but not with previously reported log P 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.