PHARMACOKINETICS AND BODY DISTRIBUTION OF LIPOSOMAL ZINC PHTHALOCYANINE IN TUMOR-BEARING MICE - INFLUENCE OF AGGREGATION STATE, PARTICLE-SIZE, AND COMPOSITION
U. Isele et al., PHARMACOKINETICS AND BODY DISTRIBUTION OF LIPOSOMAL ZINC PHTHALOCYANINE IN TUMOR-BEARING MICE - INFLUENCE OF AGGREGATION STATE, PARTICLE-SIZE, AND COMPOSITION, Journal of pharmaceutical sciences, 84(2), 1995, pp. 166-173
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.