Increasing stiffness promotes pulmonary retention of ligand-directed dexamethasone-loaded nanoparticle for enhanced acute lung inflammation therapy.

ABSTRACT: Inhaled nanoparticles (NPs) need to penetrate the bronchial mucosa to deliver drug payloads deeply in the lung for amplified local therapy. However, the bronchial mucociliary barrier eliminates NPs rapidly, which considerably limits their mucosal penetration. In this study, we find that surface ligand modification and stiffness adjustment of NPs contribute to the significantly enhanced bronchial mucosal absorption and pulmonary retention of inhaled drugs. We utilize neonatal Fc receptor ligand (FcBP) to modify the rationally designed low stiffness NPs (Soft-NP) and high stiffness NPs (Stiff-NP) to target bronchial mucosa. In an acute lung inflammation rat model, after intranasal administration with dexamethasone-loaded NPs, Stiff-NP endowed with FcBP displays superior therapeutic effects.

SUBMITTER: Yu Y 

PROVIDER: S-EPMC9253482 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature