PHOTODYNAMIC DAMAGE BY LIPOSOME-BOUND PORPHYCENES - COMPARISON BETWEEN IN-VITRO AND IN-VIVO MODELS

Photodynamic efficacy of four tetrakis(methoxyethyl)porphycene (TMPn) derivatives encapsulated in liposomes, was studied in vitro and in viv o. Fluorescence and absorption measurements were used to determine agg regation in dipalmitoyl phosphatidylcholine (DPPC) Liposomes; no spect ral changes were found when dissolving in an organic solution or in an aqueous dispersion of DPPC liposomes. This indicates that the porphyc enes were located in the lipophilic bilayer of the liposomes. Fluoresc ence quenching experiments with I- showed, specifically, that porphyce nes located in the liposome bilayer at various depths, according to th e hydrophilicity of the porphycene side chains, Dose-response relation s were established: increasing porphycene concentration or light dose enhanced the damage proportionally. In cultured MDCK cells, photodynam ic damage was in accordance with location: a porphycene 'buried' insid e the bilayer did not cause damage to the cell culture. PDT efficacy w as tested also in vivo by the damage: to blood vessels of the chorioal lantoic membrane (CAM) of the fertilized chick embryo. Unlike in the i n vitro case, the porphycene 'buried' inside the bilayer did cause sig nificant photodynamic damage in vivo. This difference suggests that in vitro photodynamic action follows contact-mediated sensitizer transfe r to cell membranes from liposomes, which remain distinct from cells, whereas in vivo the photosensitizer is delivered to tissue via fusion of liposomes with endothelial cell membranes. (C) 1998 Elsevier Scienc e S.A.