EFFECT OF DENSITY-GRADIENTS ON THE BINDING OF PHOTOSENSITIZING AGENTSTO PLASMA-PROTEINS

The binding of photosensitizing agents to low-density lipoprotein is c onsidered an important factor in tumor localization. We examined the a ffinity of a group of photosensitizers, varying in charge and hydropho bicity, for LDL, under conditions designed to determine whether the hi gh salt: concentration involved in conventional KBr gradients affected the results. Density-gradients containing KBr vs D2O were evaluated; the latter can delineate VLDL and LDL from other plasma components, wh ile the KBr gradient readily resolved VLDL, LDL, HDL and albumin, Dist ribution of the photosensitizers to plasma fractions was assessed, alo ng with the effect of Cremophor EL, an emulsifier used for formulation of water-insoluble drugs, Both the D2O and KBr gradients provided sim ilar results with regard to the affinity of anionic, neutral or cation ic photosensitizers for LDL, The use of Cremophor EL for drug formulat ion was associated with an altered electrophoretic lipoprotein profile . In some cases, affinity of CRM-solubilized sensitizers for plasma co mponents varied with the density-gradient employed, The high salt conc entration used in density-gradient fractionation had little effect on the affinity of photosensitizing agents to low-density lipoprotein but may introduce artifacts when emulsifiers are used in drug formulation .