Targeted Redox Balancing through Pulmonary Nanomedicine Delivery Reverses Oxidative Stress Induced Lung Inflammation

Non-invasive delivery of drugs is important for the reversal of respiratory diseases essentially by-passing metabolic pathways and targeting large surface area of drug absorption. Here, we study the inhalation of a redox nano medicine namely citrate functionalized Mn₃O₄ (C-Mn₃O₄) duly encapsulated in droplet evaporated aerosols for the balancing of oxidative stress generated by the exposure of Chromium (VI) ion, a potential lung carcinogenic agent. Our optical spectroscopic in-vitro experiments demonstrates the efficacy of redox balancing of the encapsulated nanoparticles (NP) for the maintenance of a homeostatic condition. The formation of Cr-NP complex as an excretion of the heavy metal is also demonstrated through optical spectroscopic and high resolution transmission optical microscopy (HRTEM). Our studies confirm the oxidative stress mitigation activity of the Cr-NP complex. A detailed immunological assay followed by histopathological studies and assessment of mitochondrial parameters in pre-clinical mice model with chromium (Cr) induced lung inflammation establishes the mechanism of drug action to be redox-buffering. Thus, localised delivery of C-Mn₃O₄ NPs in the respiratory tract via aerosols can act as an effective nanotherapeutic agent against oxidative stress induced lung inflammation.