Inhalable microparticles embedding hyaluronic acid-coated chitosan nanoparticles: fabrication and evaluation for preferential accumulation of montelukast in the lung.

The study aimed to prepare nanoembedded microparticles for pulmonary delivery of montelukast. The nanoparticles were synthesised by ionic gelation method and characterised for physicochemical properties. The nanoembedded microparticles fabricated via freeze drying method were evaluated for their physicochemical properties, drug release, aerodynamic performance and pharmacokinetic parameters in male Sprague Dawley rats. The hyaluronic-coated chitosan nanoparticles with particle size of 276.221 ± 08.232 nm, PDI of 0.397 ± 0.007, zeta potential of 14.101 ± 0.107 mV, drug content of 22.781 ± 1.002 µg/mg, and a triangular structure were embedded within microparticles. The sustained release of montelukast from nanoembedded microparticles was attributed to slow dissolution of chitosan at lung pH. The lactose-embedded nanoparticles had higher fine particle fraction (FPF: 31.37 ± 1.29) as compared to mannitol-embedded nanoparticles (FPF: 25.053 ± 0.93) due to spherical compact structure. The microparticles have lower AUC_0-t (835-856 µg.h/ml) compared to montelukast solution (1488 µg.h/ml), confirming preferential accumulation of microparticles in the lung.