Determination of liposome permeability of ionizable carbamates of

? RAVIOLO MA, SANCHEZ JM, BRIÑÓN MC AND PERILLO MA.

COLLOIDS AND SURFACES B-BIOINTERFACES

ELSEVIER SCIENCE BV

Año: 2008 p. 188 - 198

0927-7765

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 timeinside 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 valuesof 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 °A3) and AZT-Ethy (450.5 °A3), 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.3) and AZT-Ethy (450.5 °A3), 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.