Preparation and evaluation of pirfenidone loaded chitosan nanoparticles pulmonary delivery for idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal disorder caused by abnormal extracellular matrix deposition, which results in increasing dyspnea and loss of pulmonary function. Pirfenidone (PFD) has antifibrotic properties that have been approved by the US FDA for the treatment of IPF. Pirfenidone is currently delivered orally, which has drawbacks like reduced bioavailability in the presence of food, gastrointestinal (dyspepsia and anorexia), and dermatological (photosensitivity) side-effects, large amount of dose, and elimination half-life of 2.4 h. This study aimed was to prepare inhalable powders containing PFD-loaded chitosan nanoparticles for sustained delivery of the drug to the lung. The quasi-solvent diffusion method was used with optimized 100 mg PFD and 100 mg chitosan (CS). An in-vitro drug release research found that increasing the amount of chitosan reduced the rate of drug release from nanoparticles. Entrapment of PFD into chitosan nanoparticles decreased with the increased concentration of stabilizer concentration. All batches produced nanoparticles with a spherical morphology confirmed by SEM and sizes ranging from 239.3 ± 1.8 to 928.7 ± 4.6 nm. The optimized nanoparticles exhibited a mean particle size of 467.33 ± 7.8 nm with a polydispersity index of 0.127 ± 0.022, zeta potential of + 34.8 ± 1.6 mV, % entrapment efficiency (39.45 ± 4.63%), % drug release after 12 h (94.78 ± 2.88%), and in-vitro deposition (81.49%). Results showed that the obtained powders had different aerosolization properties. The particle size of nanoparticles reduced, and the process yield, extra-fine particle fraction, geometric standard diameter, and fine particle fraction increased significantly. Stability study showed, there are no aggregation observed and stable for six month study. Prepared pirfenidone-loaded chitosan nanoparticles can be result of 6 months of stability studies that give details that there was no significant aggregation of PFD-loaded CS NPs and the spherical shape particle with smooth surface as per SEM studies. Hence, PFD-loaded CS NPs can be a suitable alternative to the currently available therapy.