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Photodynamic Activities and Skin Photosensitivity of the Bis(dimethylthexylsiloxy)silicon 2,3-naphthalocyanine in Mice

Photodynamic Activities and Skin Photosensitivity of the Bis(dimethylthexylsiloxy)silicon 2,3-naphthalocyanine in Mice

N Brasseur, R Ouellet, K Lewis, W R Potter, J E van Lier

Photochem Photobiol. 1995 Dec;62(6):1058-65.

PMID: 8570740

Abstract:

The photodynamic therapy (PDT) activity of the bis(dimethylthexylsiloxy)silicon 2,3-naphthalocyanine (SiNc 8) was evaluated against the EMT-6 tumor implanted intradermally in BALB/c mice. The SiNc 8 was formulated in aqueous emulsions based on Cremophor EL or Solutol HS 15. The formulation was shown to affect plasma clearance and overall pharmacokinetics. Compared to Cremophor, Solutol promoted rapid plasma clearance and high liver retention of the dye, combined with a slight increase of dye tumor concentrations. The PDT action spectrum for tumor response of SiNc 8 in Cremophor (190 mW cm-2, 200 J cm-2, 24 h postinjection [p.i.] of 1 mumol kg-1) showed a maximum at 780 nm, which corresponds 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 mumol 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 resulted in complete tumor regression in 80% of the animals without adverse effects to adjacent tissues, while at 72 h p.i. PDT induced no tumor response with Cremophor and only a partial response with Solutol. At the latter time point, plasma dye clearance was nearly complete while tumor tissue levels remained high, suggesting that tumor response correlates with plasma rather than tumor dye levels. Skin sensitivity of SKhI mice to solar-simulated radiation was lower with SiNc 8 as compared to Photofrin. Our data suggest the potential of SiNc 8 as a far-red absorbing photosensitizer in clinical PDT.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP23627896	2,3-Naphthalocyanine		23627-89-6	Price

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