THE EFFECT OF DIFFERENT LIPOSOMAL FORMULATIONS ON THE INTERACTION OF ZN(II)-PHTHALOCYANINE WITH ISOLATED LOW AND HIGH-DENSITY-LIPOPROTEINS

Several phthalocyanines exhibit a high affinity for tumour tissues and upon red-light irradiation originate a photosensitized process leading to tumour necrosis, This study was designed to define the role of different liposomal formulations in modulating the affinity of Zn(II)-phthalocyanine (ZnPc) for isolated low- and high-density lipoproteins (LDL, HDL). This information is important as the uptake of hydrophobic photosensitizers by tumour tissues can be enhanced by their association with LDL, The kinetics and efficiency of ZnPc association with LDL and HDL as well as the redistribution of ZnPc between the lipoproteins were studied by salt gradient ultracentrifugation and spectrophotometric analyses of the isolated lipoproteins. The formation of the photosensitizer-lipoprotein complexes in the plasma is affected by the vehicle utilized for the drug delivery, ZnPc in I 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/1,2-dioleoyl-sn-glycero-3-L-serine and 1,2-dimyristoyl-sn-glycero-3-phosphocholine liposomes is transferred to lipoproteins within a few minutes, while the transfer of ZnPc from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine liposomes reaches a steady state value in a time scale of 5-6 hr, The binding capacity of LDL for ZnPc can be as high as about 60 phthalocyanine molecules per protein particle, although the final value is affected by the phospholipid composition of the Liposomes and the liposome/lipoprotein ratio. HDL have a lower binding capacity (max. about 3 ZnPc/protein) as shown by studies of interlipoprotein transfer of the photosensitizer. The present findings indicate that the association of photosensitizers with lipid-based delivery systems, besides being necessary for water-insoluble compounds, affects their distribution among lipoproteins. Liposomes which are in a fluid state at the temperature of 37 degrees C enhance the binding of ZnPc to LDL, which should increase the selectivity of tumour targeting by the phthalocyanine owing to the efficient receptor-mediated endocytosis of LDL by several types of malignant cells.