Novel multifunctional
photosensitizers (MFPSs), 5,10,15-tris(4-
N-methylpyridinium)-20-(4-phenylthio)-[21H,23H]-
porphine trichloride (PORTH) and 5,10,15-tris(4-
N-methylpyridinium)-20-(4-(butyramido-methylcysteinyl)-hydroxyphenyl)-[21H,23H]-
porphine trichloride (PORTHE), derived from 5,10,15-Tris(4-methylpyridinium)-20-phenyl-[21H,23H]-
porphine trichloride (
Sylsens B) and designed for treatment of
onychomycosis were characterized and their functionality evaluated. MFPSs should function as nail penetration enhancer and as
photosensitizer for photodynamic treatment (
PDT) of
onychomycosis. Spectrophotometry was used to characterize MFPSs with and without 532 nm continuous-wave 5 mW cm(-2)
laser light (± argon/
mannitol/
NaN3 ). Nail penetration enhancement was screened (pH 5, pH 8) using water uptake in nails and fluorescence microscopy.
PDT efficacy was tested (pH 5, ± argon/
mannitol/
NaN3 ) in vitro with Trichophyton mentagrophytus microconida (532 nm, 5 mW cm(-2) ). A light-dependent absorbance decrease and fluorescence increase were found, PORTH being less photostable.
Argon and
mannitol increased PORTH and PORTHE photostability;
NaN3 had no effect.
PDT (0.6 J cm(-2) , 2 μm) showed 4.6 log kill for PORTH, 4.4 for
Sylsens B and 3.2 for PORTHE (4.1 for 10 μm).
Argon increased PORTHE, but decreased PORTH
PDT efficacy;
NaN3 increased
PDT effect of both MFPSs whereas
mannitol increased
PDT effect of PORTHE only. Similar penetration enhancement effects were observed for PORTH (pH 5 and 8) and PORTHE (pH 8). PORTHE is more photostable, effective under low
oxygen conditions and thus realistic candidate for
onychomycosis PDT.