zn(ii)-phthalocyanine and 1-palmitoyl-2-oleoylphosphatidylcholine

Photodynamic therapy exploits the light-activation of a photosensitizer to cause cytotoxicity. Liposomes can be used to deliver hydrophobic photosensitizers to bacteria. Positively charged dioleoyltrimethylammoniumpropane:palmitoyloleoylphosphatidylcholine (1:1) liposomes bound quantitatively to the periodontal pathogen, Porphyromonas gingivalis. Following illumination, free and liposomal zinc phthalocyanine reduced the colony-forming unit (CFU) to 65 percent and 23 percent of controls, respectively. Thus, localization of the photosensitizer at the surface of bacteria via liposome binding enhanced the photodynamic cytotoxicity of zinc phthalocyanine.

Topics: Bacterial Adhesion; Colony Count, Microbial; Fatty Acids, Monounsaturated; Humans; Indoles; Isoindoles; Liposomes; Membrane Proteins; Organometallic Compounds; Periodontitis; Phosphatidylcholines; Photochemotherapy; Photosensitizing Agents; Porphyromonas gingivalis; Protein Binding; Quaternary Ammonium Compounds; Zinc Compounds

We have studied the interaction of small unilamellar liposomes containing zinc(II)-phthalocyanine (Zn-Pc) with human plasma lipoproteins. High-, low- and very low-density lipoproteins (HDL, LDL and VLDL), were purified from plasma and combined in amounts reflecting their natural abundance in plasma. After short periods of incubation at 37 degrees C, the bulk of Zn-Pc was incorporated into HDL and LDL; very little 14C-labelled palmitoyl oleoyl phosphocholine, the most abundant phospholipid in the formulation, was associated with lipoproteins. When liposomes were incubated in pooled plasma, 73%-85% of Zn-Pc and 27%-34% of radiolabelled phospholipid were recovered with HDL and LDL, indicating a possible role for plasma lipid transfer proteins in the incorporation of phospholipid into lipoproteins. Some Zn-Pc was also found in association with VLDL. The buoyant density of Zn-Pc liposomes increased in a dose-dependent fashion when the particles were incubated with plasma, and it is suggested that this was due, at least in part, to opsonization of liposomes by plasma proteins.

Topics: Autoradiography; Carbon Radioisotopes; Centrifugation, Density Gradient; Electrophoresis, Agar Gel; Humans; Indoles; Iodine Radioisotopes; Isoindoles; Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Liposomes; Organometallic Compounds; Phosphatidylcholines; Zinc Compounds

The interaction of human low density lipoprotein (LDL) and small unilamellar liposomes containing the photosensitiser zinc(II)-phthalocyanine (Zn-Pc) was studied in vitro to determine if Zn-Pc could be directly incorporated into the lipoprotein in the absence of other serum components. Incubation of LDL with increasing concentrations of liposomes resulted in a progressive increase in the net negative charge of LDL as determined by agarose gel electrophoresis and both Zn-Pc and liposomal phospholipid were incorporated into the modified LDL particles. Gel chromatography experiments indicated an increase in the molecular mass of modified LDL and immunoaffinity chromatography provided evidence that apoprotein B epitopes on modified LDL were unable to bind to antibody. The study indicated that the liposomal components could be selectively incorporated into LDL by a process that did not appear to involve either aggregation or fusion of particles.

Topics: Carbon Radioisotopes; Chromatography, Affinity; Chromatography, Ion Exchange; Electrophoresis, Agar Gel; Humans; Indoles; Isoindoles; Lipoproteins, LDL; Liposomes; Organometallic Compounds; Phosphatidylcholines; Zinc; Zinc Compounds