Title : Co-delivery of antiviral and anti-inflammatory agents via dry powder inhalation for viral pneumonia
Abstract:
Viral pneumonia remains a significant global health challenge, with current therapeutic approaches often limited by inadequate drug delivery to the primary infection site and the need to address both viral replication and excessive inflammation simultaneously. We present an innovative pulmonary drug delivery system designed to overcome these limitations through targeted co-delivery of antiviral and anti-inflammatory agents directly to the lungs.
Our approach centers on a rationally designed dry powder inhalation (DPI) formulation that combines zanamivir, a neuraminidase inhibitor, with budesonide, a potent glucocorticoid. This dual-drug delivery system leverages the advantages of pulmonary administration to achieve high local drug concentrations at the infection site while minimizing systemic exposure and associated side effects. The DPI formulation was engineered with optimized particle size distribution and aerodynamic properties to ensure deep lung penetration and efficient deposition in the lower respiratory tract.
Comprehensive pharmacokinetic evaluation in rats demonstrated sustained retention of both active agents in lung tissue, with favorable distribution profiles that support once- or twice-daily dosing. The formulation exhibited excellent aerosolization performance with appropriate fine particle fraction for effective pulmonary delivery.
Therapeutic efficacy was rigorously assessed in an H1N1-infected mouse model of viral pneumonia. The combination DPI treatment achieved superior outcomes compared to monotherapy with either agent, significantly reducing viral burden and inflammatory mediators while markedly improving lung histopathology. Importantly, safety evaluations confirmed excellent local tolerability without adverse effects on pulmonary function, supporting the clinical translatability of this delivery approach.
This work demonstrates how advanced drug delivery strategies can transform therapeutic outcomes in respiratory infections. By enabling simultaneous, site-specific delivery of complementary therapeutic agents, our DPI system addresses the complex pathophysiology of viral pneumonia more effectively than conventional systemic or single-agent approaches. This platform technology holds promise for broader application to other respiratory diseases requiring combination therapy, offering a practical solution for site-specific pulmonary drug delivery.
