Photodynamic and Nail Penetration Enhancing Effects of Novel Multifunctional Photosensitizers Designed for The Treatment of Onychomycosis

Novel multifunctional photosensitizers ( MFPS s), 5,10,15‐tris(4‐ N ‐methylpyridinium)‐20‐(4‐phenylthio)‐[21 H ,23 H ]‐porphine trichloride ( PORTH ) and 5,10,15‐tris(4‐ N ‐methylpyridinium)‐20‐(4‐(butyramido‐methylcysteinyl)‐hydroxyphenyl)‐[21 H ,23 H ]‐porphine trichloride ( PORTHE ), derived from 5,10,15‐Tris(4‐methylpyridinium)‐20‐phenyl‐[21 H ,23 H ]‐porphine trichloride (Sylsens B) and designed for treatment of onychomycosis were characterized and their functionality evaluated. MFPS s should function as nail penetration enhancer and as photosensitizer for photodynamic treatment ( PDT ) of onychomycosis. Spectrophotometry was used to characterize MFPS s with and without 532 nm continuous‐wave 5 mW cm −2 laser light (± argon/mannitol/NaN 3 ). 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/NaN 3 ) 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; NaN 3 had no effect. PDT (0.6 J cm −2 , 2 μ m ) showed 4.6 log kill for PORTH , 4.4 for Sylsens B and 3.2 for PORTHE (4.1 for 10 μ m ). Argon increased PORTHE , but decreased PORTH PDT efficacy; NaN 3 increased PDT effect of both MFPS s 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 .