Antifungal activity of oily core PEGylated PLGA nanocapsules loaded with Penicillium oxalicum fungal extract: in vitro, in vivo, and in silico study

Abstract The rise of difficult-to-treat fungal infections necessitates novel therapeutic strategies. In this study, endophytic fungi were isolated from Acalypha hispida leaves and molecularly identified as Penicillium oxalicum via 18S rRNA sequencing. LC–MS/MS analysis of the fungal extract revealed major bioactive compounds, including linoleic acid, sinapinic acid, alternariol monomethyl ether, ellagic acid, and kaurenic acid. Oily-core poly (ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) nanocapsules (PEGylated PLGA NCs) were developed to encapsulate the fungal extract, improving stability and bioavailability. The PEGylated PLGA NCs exhibited controlled particle size, positive surface charge, and spherical morphology. In vitro, the PEGylated PLGA NCs demonstrated antifungal activity against Candida albicans with inhibition zones of 10–14 mm. In vivo, treatment significantly improved histological features of the kidney, liver, and spleen, and reduced tumor necrosis factor-alpha and cyclooxygenase-2 expression. In silico studies further confirmed the potential of the major compounds of the fungal extract to inhibit C. albicans aspartic proteinases SAP4-6. These findings suggest that PEGylated PLGA NCs loaded with P. oxalicum extract represent a promising antifungal therapeutic strategy.