Therapeutic potential of dexamethasone Nano chitosan synthesized from chitosan as a novel treatment of pulmonary fibrosis in C57BL/6 mice

Abstract

ABSTRACT Back ground: Pulmonary fibrosis is an irreversible disease with excessive scarring and fibrosis of lung tissue. Glucocorticoid therapy of dexamethasone attenuates lung inflammation with severe adverse effects. Subsequently, synthesizing Nano chitosan from chitosan macromolecule and loading dexamethasone onto Nano chitosan particles have shown improved pharmacokinetics of dexamethasone. Purpose: The aim of this study was to prepare and characterize dexamethasone Nano chitosan particles chemically and then to evaluate the effectiveness of loading dexamethasone onto Nano chitosan as a treatment of pulmonary injury induced by bleomycin-induced in C57BL/6 mice. Results: This study elucidated significant elevations of serum malondialdehyde and lactate dehydrogenase with an increased lung tissue inflammatory mediators, collagen profile, Caspase-3, and MUC5AC gene expressions. This was accompanied by a significant elevation in total and differential leukocyte counts in bronchoalveolar lavage fluid. Besides, there were recognized histological and histopathological alterations in lung tissue sections following both 14 and 28 days of bleomycin instillation. Consequently, treatment of lung injury by dexamethasone alone or dexamethasone loaded onto Nano chitosan particles revealed a significant reduction of MDA and LDH, a decline in lung tissue inflammatory mediators, collagen profile, Caspase-3, and MUC5AC gene expressions. This was accompanied by a significant reduction in total and differential leukocyte counts in bronchoalveolar lavage fluid. However, loading dexamethasone onto Nano chitosan provided novel insights in pulmonary injury treatment