ARTIFICIAL MEMBRANES 247 -11 •, -2 E E -4 -9 -8 -7 -6 -5 -4 -3 -2 log P (human skin) Figure 6. Correlation between permeabilities of markers across BSA membranes and across human skin. stratum corneum with which the lipid bilayer matrix may interact and result in a more cohesive membrane. The BSA-treated membrane, after calcium chloride treatment, exhibited markedly higher resistance to the permeation of sucrose compared to non- treated membranes. It was also confirmed that heat treatment at 80øC of blank filters alone or of lipid membranes without BSA treatment did not lead to reduction of sucrose permeation across these membranes. It was also observed that both BSA and calcium chloride treatment protocols were essential to the generation of model membranes with high barrier properties to hydrophilic drug markers. Treatment of lipid-laden filters with either BSA only or calcium chloride alone did not suffice. This suggests that the model membrane obtained after the combined treatment protocols probably incorporates interactions between the protein and lipid bilayers via calcium-mediated linkages. It would be necessary to carry out extensive structural investigations by electron mi- croscopy and other spectroscopic methods to define the interactions at a molecular level. It is clear, however, that the model membranes prepared in this fashion possess excellent potential to screen a variety of compounds for permeation characteristics across human or animal skin. The excellent correlations of permeability values of several markers across the BSA-model membranes with octanol-water partition coefficients (Fig 5, r 2 = 0.92) and with available data on their permeability across human skin (Fig 6, r 2 = 0.97)

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