Lung-Targeted Itraconazole Delivery Using PVA-Based Nano-in-Microparticles for Improved Treatment of Pulmonary Aspergillosis.

Purpose: Pulmonary aspergillosis (PA) presents a substantial therapeutic challenge, especially in immunocompromised patients, where conventional systemic treatments like oral and intravenous routes often result in limited efficacy and increased adverse effects. This study focuses on the development and evaluation of an inhalable itraconazole (ITZ) formulation within a nanoparticles-in-microparticles (NIM) system. Methods: Polyvinyl alcohol 500 (PVA), used in varying concentrations, played a crucial role as a stabilizer in both the wet bead milling and spray drying processes, enhancing drug release and aerodynamic performance. The influence of PVA ratios on drug penetration into pulmonary mucus and interactions with pulmonary defense mechanisms were thoroughly investigated through in-vitro simulations. Results: Pharmacokinetic analysis in Conclusion: The incorporation of PVA in NIM technology demonstrated not only improved pulmonary targeting and drug release but also minimized systemic toxicity, highlighting the potential of nanoparticle-based inhalation systems in treating respiratory fungal infections like aspergillosis. These findings emphasize the pivotal role of PVA in the formulation, stability, and therapeutic efficacy of NIM-based drug delivery systems for pulmonary applications, advancing the use of nanoparticle technology in respiratory drug delivery.