PHOTODYNAMIC ACTIVITIES AND SKIN PHOTOSENSITIVITY OF THE BIS(DIMETHYLTHEXYLSILOXY)SILICON 2,3-NAPHTHALOCYANINE IN MICE

The photodynamic therapy (PDT) activity of the bis(dimethylthexylsilox y) silicon 2,3-naphthalocyanine (SiNc 8) was evaluated against the EMT -6 tumor implanted intradermally in BALB/c mice. The SiNc 8 was formul ated in aqueous emulsions based on Cremophor EL or Solutol HS 15. The formulation was shown to affect plasma clearance and overall pharmacok inetics. Compared to Cremophor, Solutol promoted rapid plasma clearanc e and high liver retention of the dye, combined with a slight increase of dye tumor concentrations. The PDT action spectrum for tumor respon se of SiNc 8 in Cremophor (190 mW cm(-2), 200 J cm(-2), 24 h postinjec tion [p.i.] of 1 mu mol kg(-1)) showed a maximum at 780 nm, which corr esponds to the absorption maximum of the monomeric dye as well as the in vivo maximum change in the ''diffuse optical density'' produced by the dye. The extent of tumor necrosis increased with augmented dye and light doses. Regardless of the formulation, at 1 h p.i. of 0.1 mu mol kg(-1) SiNc 8, PDT efficiency (190 mW cm(-2), 400 J cm(-2)) was high but accompanied by severe damage to normal tissues, at 24 h p.i. PDT r esulted in complete tumor regression in 80% of the animals without adv erse effects to adjacent tissues, while at 72 h p.i. PDT induced no tu mor response with Cremophor and only a partial response with Solutol. At the latter time point, plasma dye clearance was nearly complete whi le tumor tissue levels remained high, suggesting that tumor response c orrelates with plasma rather than tumor dye levels. Skin sensitivity o f SKhI mice to solar-simulated radiation was lower with SiNc 8 as comp ared to Photofrin(R). Our data suggest the potential of SiNc 8 as a fa r-red absorbing photosensitizer in clinical PDT.