A novel topical delivery of biphasic Janus nanoparticles loaded with miconazole nitrate and berberine hydrochloride for antifungal therapy against Candida albicans

This study develops and characterizes biphasic Janus nanoparticles (JNPs) for the co-delivery of miconazole nitrate (MCN) and berberine hydrochloride (BER), aiming to enhance antifungal efficacy through combinatorial therapy against superficial fungal infections. JNPs were synthesized using single-phase emulsion (O/W-S) and double-phase emulsion (W/O/W) methods, and their physicochemical properties were characterized, including size distribution, polydispersity, surface charge, and encapsulation efficiency. In vitro drug release profiles of MCN and BER from JNPs were evaluated, along with a hydrogel (HG) formulation incorporating optimized JNPs for topical application. Solubility assessments, Fourier transform infrared (FT-IR) spectroscopy for compatibility analysis, and antifungal activity testing against Candida albicans using the agar well diffusion method were also performed. JNPs exhibited a unique dumbbell-shaped morphology, achieving encapsulation efficiencies of 90.32% for MCN and 71.13% for BER in the W/O/W method. In vitro drug release studies showed cumulative releases of 97.52% for MCN and 90.23% for BER over 24 h in the JNP-HG formulation. The hydrogel, with a pH of 6.75 ± 0.13 and exhibiting non-Newtonian pseudoplastic behaviour, demonstrated excellent spreadability. Antifungal tests revealed significant efficacy of the co-loaded JNPs in the hydrogel, showing larger inhibition zones compared to individual drugs due to synergism. This research introduces a novel platform employing JNPs for the combinatorial delivery of hydrophilic and hydrophobic drugs, facilitating sustained release and offering promising therapeutic potential for antifungal agents. Future studies should evaluate its in vivo performance and explore diverse combinatorial therapies.