Hydralazine potentiates the antiproliferative effect of photodynamic therapy on Candida albicans and Candida parapsilosis in vitro

The incidence of drug-resistant Candida infections is increasing globally, emphasizing the need for novel antifungal strategies. Photodynamic therapy (PDT), which generates reactive oxygen species through appropriate light-activated photosensitizers, represents a promising alternative for superficial infections. This study investigated the effect of the epigenetic drugs sodium butyrate (NaBut) and hydralazine (HLZ) combined with PDT on the growth of Candida spp. The minimum inhibitory concentrations (MICs) for NaBut, HLZ and PDT alone were assessed against C. albicans, C. parapsilosis, C. glabrata and C. tropicalis. Candida cells were then exposed to sub-inhibitory concentrations of NaBut or HLZ (50% or 75% MIC), incubated with the aluminum-phthalocyanine chloride nanoemulsion (AlPc‑NE) photosensitizer, and irradiated at 660 nm. C. glabrata was the species most susceptible to NaBut (128 mM) and HLZ (0.46 mM), followed by C. albicans (256 mM NaBut, 1.5 mM HLZ). The C. albicans cells were the most susceptible to PDT alone (12.5 nM AlPc‑NE), followed by C. parapsilosis (25 nM AlPc‑NE). Previous exposure to HLZ significantly increased the efficacy of PDT on inhibiting the growth of these last two species. These findings may contribute to the development of new therapeutic strategies against superficial Candida infections.