A comparative pulmonary pharmacokinetic study of budesonide using polymeric nanoparticles targeted to the lungs in treatment of asthma

Abstract

Budesonide (BUD) exhibits a very low bioavailability to lungs which makes it less favourable as an inhalational dosage form. Developed-Nanoparticles (NPs) [coated with chitosan (CS)] i.e. BUD-NPs are intended to enhance lungs-BUD bioavailability, aerosolization, lungs deposition as well as pharmacokinetic profile for BUD-NPs. BUD-NPs were developed through single-emulsification-solvent-evaporation technique. Characterisation of BUD-NPs was done for particle size, zeta potential, size distribution, encapsulation efficiency, and in vitro drug-release. A particle size (196.4 ± 10.05 nm) with smooth and spherical shape alongwith zeta potential (11.8 ± 0.91 mV) and drug-content (44.64 ± 2.91 µg/mg) was observed. Ultra-high-performance-liquid-chromatography-mass spectroscopy (UHPLC-MS/MS) study was successfully applied for comparative effects of BUD-NPs lungs bioavailability via major delivery routes, and their biological effects. The NPs i.e. BUD-NPs revealed more bioavailability and in vivo lung deposition in animal model as compared to oral (3.0-times-higher) and i.v. (2.0-times-higher). BUD 0.75 min and 431.61/323.16 m/z whereas Fluticasone (IS) 1.16 min and 501.42/313.31 m/z, elution time and transition respectively. The CS-approach was successfully designed and safely delivered BUD to the lungs without causing any risk. BUD-NPs did not cause any toxicity, it showed safety and have no obvious toxic-effects on the rat’s lungs and does not produce any mortality followed by no abnormal findings in the treated-rats.