Polymeric nano-in-microparticles for pulmonary delivery of remdesivir against SARS-CoV-2

Abstract

The COVID-19 pandemic underscored the urgent need for advanced drug delivery systems to enhance the safety and efficacy of existing antiviral therapies. This study presents an inhalable powder formulation of remdesivir (RDV) using polymeric nano-in-microparticles for pulmonary administration. RDV was nanoencapsulated in a polycaprolactone (PCL) matrix via emulsion–diffusion–solvent evaporation and stabilized with DPPC and Pluronic F127, resulting in nanoparticles (RDV-PCL-NP) of 184 ± 11 nm and 87% encapsulation efficiency. Cytotoxicity assays in Vero E6 cells confirmed the RDV-PCL-NP safety at therapeutic concentrations, with a marked reduction in the SARS-CoV-2 viral load at 5 µM RDV. The nanoparticles were spray dried with lactose, yielding a dry powder (RDV-PCL-MP) with 63% process yield. Physicochemical characterization (SEM, FTIR, DRX, DSC/TGA, laser diffraction) confirmed uniform particle size and stability (1–5 µm) of the RDV-PCL-MP inhalable powder. In vitro lung deposition studies showed 40% fine fraction and 39% respirable fraction. These findings support the potential of RDV-loaded nano-in-microparticles as a scalable pulmonary delivery platform to improve COVID-19 treatment.