Physicochemical Characterization and in Vitro Aerosol Performance of a Nebulizable PLGA Micafungin Nanoformulation for Sino-Pulmonary Fungal Infections

Abstract

Pulmonary fungal infections remain a major therapeutic challenge, and localized drug delivery through inhalation offers the potential to improve treatment efficacy while reducing systemic adverse effects. The present study aimed to characterize an optimized nebulizable micafungin-loaded PLGA nanoformulation for pulmonary drug delivery. The optimized formulation, developed using a 2³ full factorial design, was evaluated for its physicochemical properties, morphological characteristics, residual solvent content, nebulization performance, and aerodynamic behavior. Particle size, polydispersity index, zeta potential, and entrapment efficiency were determined, while transmission electron microscopy (TEM), polarized light microscopy (PLM), and gas chromatography–mass spectrometry (GC–MS) were employed for morphological and residual solvent analysis. Nebulization performance and aerosol characteristics were further assessed using a vibrating mesh nebulizer and cascade impactor, respectively. The optimized nanoformulation exhibited desirable physicochemical and aerosolization characteristics, efficient nebulization performance, and no detectable residual organic solvent, indicating its suitability for pulmonary administration. These findings demonstrate the potential of the developed micafungin-loaded PLGA nanoformulation as a promising inhalable antifungal drug delivery system for the management of pulmonary fungal infections.