Controlled targeting of different subcellular sites by porphyrins in tumour-bearing mice.
Unilamellar liposomes of dipalmitoyl-phosphatidylcholine can incorporate various porphyrins in either the phospholipid bilayer or the internal aqueous compartment depending on the water-/lipo-solubility of the drug. Intraperitoneal injection of the liposome-bound porphyrins to mice bearing a MS-2 fibrosarcoma results in remarkably more efficient tumour targeting than that obtained by administration of the same porphyrins dissolved in homogeneous aqueous solution. Moreover, also water-insoluble porphyrins can be transported to the tumour via liposomes. Fractionation of liver and neoplastic cells indicates that the subcellular distribution of liposome-delivered porphyrins is also dependent on their solubility properties: thus, relatively polar porphyrins, such as tetra(4-sulfonatophenyl)porphine and uroporphyrin, are mainly recovered from the soluble fraction, whereas hydrophobic porphyrins, such as haematoporphyrin or porphyrin esters, preferentially partition in the cytoplasmic membrane. As a consequence, different subcellular sites can be targeted by porphyrins and possibly photodamaged through a suitable choice of the drug-carrier system.
D000818:Animals; D004347:Drug Interactions; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism*; D006415:Hematoporphyrins / Q000378:metabolism; D007700:Kinetics; D008081:Liposomes / Q000008:administration & dosage* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011166:Porphyrins / Q000378:metabolism* / Q000627:therapeutic use; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution
D006415:Hematoporphyrins; D008081:Liposomes; D011166:Porphyrins