Zinc octa-n-alkyl phthalocyanines in photodynamic therapy: photophysical properties, accumulation and apoptosis in cell cultures, studies in erythrocytes and topical application to Balb/c mice skin.
Two octa-substituted phthalocyanines, namely 1,4,8,11,15,18,22,25-octakis(decyl)phthalocyaninato zinc(II) (ZnODPc) and 1,4,8,11,15,18,22,25-octakis(pentyl)phthalocyaninato zinc(II) (ZnOPPc), were investigated for their use in photodynamic therapy (PDT) after topical application. Both substances exhibited favourable properties as photosensitisers in vitro: absorption maxima around 700 nm with absorption coefficients of about 190000 (M(-1) cm(-1)), a singlet oxygen quantum yield of 0.47 +/- 0.02 (ZnODPc), and good accumulation in keratinocytes and fibroblasts. Cell death after phthalocyanine-photosensitisation appeared to occur mainly via apoptosis. The in vivo experiments demonstrated a good accumulation of the phthalocyanines after topical application in a tetrahydrofuran-azone formulation onto the dorsal skin of Balb/c mice: [(4.6-4.7) +/- 1.0]% of deposited dye could be recovered after 3 h from deposition. ZnODPc showed significantly better skin-photosensitising properties than ZnOPPc and is therefore a potential candidate for the treatment of psoriasis.
Kaestner
Lars
L
Gentian AS, Belsetsvingen 39, 1348 Rykkinn, Norway. biophysics@web.de
Cesson
Mara
M
Kassab
Kawser
K
Christensen
Terje
T
Edminson
Paul D
PD
Cook
Michael J
MJ
Chambrier
Isabelle
I
Jori
Giulio
G
D016475:3T3 Cells; D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D054833:Isoindoles; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D026082:Singlet Oxygen / Q000737:chemistry; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013053:Spectrophotometry / Q000379:methods; D017967:Zinc Compounds
D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; D026082:Singlet Oxygen; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases