PHARMACOKINETICS AND BODY DISTRIBUTION OF LIPOSOMAL ZINC PHTHALOCYANINE IN TUMOR-BEARING MICE - INFLUENCE OF AGGREGATION STATE, PARTICLE-SIZE, AND COMPOSITION

The pharmacokinetics and body distribution of zinc phthalocyanine (ZnP c) intravenously administered in liposomes composed of ZnPc, 1-palmito yl-2-oleoylphosphatidylcholine (POPC), and 1,2-dioleoylphosphatidylser ine (OOPS) (1:90:10 or 1:70:30 w/w) to tumor (Meth A sarcoma) bearing mice were studied. It was found that aggregation of ZnPc in the liposo mes (i) increases the clearance rate of the dye from plasma, (ii) lowe rs the maximal dye concentration in tumor tissue, and (iii) increases the maximal dye concentration in the liver. In addition, aggregated dy e is hardly eliminated from the liver and monomeric dye is eventually completely eliminated from this organ. Liposomes in the size range of 48-123 nm, containing the dye with the same aggregation state, showed the same pharmacokinetics and body distribution of the dye. The PS-con tent of the ZnPc liposomes (POPC alone versus POPC/OOPS 7:3) did not i nfluence tumor, liver, and plasma pharmacokinetics during the studied time intervals. Free flow electrophoretic analysis showed in lyophilis ates of ZnPc liposomes containing aggregated ZnPc the presence of two distinct populations differing in size, aggregation state of the dye, and PC/PS and ZnPc/phospholipid ratio. The liposomal formulation with monomeric ZnPc has a compositional homogeneity and demonstrated select ivity and reached high uptake in tumors, 48 h after intravenous admini stration and appears promising for photodynamic therapy.