Brazilian Green Propolis Extract-Loaded Poly(Ε-Caprolactone) Nanoparticles Coated with Hyaluronic Acid: Antifungal Activity in a Murine Model of Vulvovaginal Candidiasis

Abstract

Brazilian green propolis extract-loaded poly(ε-caprolactone) nanoparticles coated with hyaluronic acid (PE-NPsHA) were developed as a therapeutic strategy to treat vulvovaginal candidiasis (VVC) and combat the growing issue of fungal resistance. The chemical composition of PE was analyzed using UHPLC-MS/MS, revealing the presence of various bioactive compounds, such as phenolic acids, flavonoids, coumarins, and quinones. These compounds were encapsulated into the polymeric matrix of NPs, as indicated by FTIR and DSC. In addition, PE-NPsHA were characterized by DLS, AFM, encapsulation efficiency (EE), and in vitro release study. They displayed a spherical morphology with a hydrodynamic diameter of 170 nm, a low polydispersity index of 0.1, a zeta potential of -28.5 mV, and an EE of 78%. The in vitro release study indicated a controlled and sustained release of PE over a period of 96 h. The in vitro and in vivo PE-NPsHA biocompatibility were investigated as well as their antifungal activity in a murine model of VVC. PE-NPsHA did not impact the HaCaT cell viability and demonstrated no signs of in vivo vaginal toxicity. PE-NPsHA exhibited in vivo antifungal efficacy, effectively eliminating Candida albicans infection. PE-NPsHA could expand the available treatment options for VVC and counteract Candida resistance to antifungal drugs.