N. Brasseur et al., PHOTODYNAMIC ACTIVITIES AND SKIN PHOTOSENSITIVITY OF THE BIS(DIMETHYLTHEXYLSILOXY)SILICON 2,3-NAPHTHALOCYANINE IN MICE, Photochemistry and photobiology, 62(6), 1995, pp. 1058-1065
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.