Enhancement of suppression oxidative stress and inflammation of quercetin by nano‐decoration for ameliorating silica‐induced pulmonary fibrosis

Abstract

Silicosis is a life‐threatening lung fibrotic disease caused by excessive inhalation of environmental exposure to crystalline silica‐containing dust, whereas achieving therapeutic cures are constrained. Antioxidation and anti‐inflammation are currently recognized as effective strategies to counteract organ fibrosis. Using naturally occurring phytomedicines quercetin (Qu) has emerged in antagonizing fibrotic disorders involving oxidative stress and inflammation, but unfortunately the hydrophilicity deficiency. Herein, chitosan‐assisted encapsulation of Qu in nanoparticles (Qu/CS‐NPs) was first fabricated for silicosis‐associated fibrosis treatment by pulmonary delivery. Qu/CS‐NPs with spherical diameters of ~160 nm, demonstrated a high Qu encapsulated capability, excellent hydrophilic stability, fantastic oxidation radical scavenging action, and outstanding controlled as well as slow release Qu action. A silicosis rat model induced by intratracheal instillation silica was established to estimate the anti‐fibrosis effect of Qu/CS‐NPs. After intratracheal administration, CS‐NPs markedly enhanced Qu anti‐fibrotic therapy efficacy, accompanying the evident changes in reducing ROS and MDA production to mitigate oxidative stress, inhibiting IL‐1β and TNF‐α release, improving lung histological architecture, down‐regulating α‐SAM levels and suppressing ECM deposition, and thereby ameliorating silica‐induced pulmonary fibrosis. Results manifested that the augmented antioxidant and anti‐inflammatory activities of Qu by CS‐NPs delivery was a result of achieving this remarkable improvement in curative effects. Combined with negligible systemic toxicity, nano‐decorated Qu may provide a feasible therapeutic option for silicosis therapy.

Natural Products-Based Inhaled Formulations for Treating Pulmonary Diseases

“…bovis and Escherichia coli DH5 alpha [ 100 ] Curcumin-loaded PLGA-nanoparticles embedded in a mannitol matrix Pulmonary infections 185.96 ± 16.79 2.88 ± 0.13 −4.71 ± 0.79 0.11 ± 0.04 ↓Staphylococcus saprophyticus subsp. bovis and Escherichia coli DH5 alpha [ 101 ] Quercetin Chitosan-assisted encapsulation of quercetin in nanoparticles Silicosis 168.19 ± 2.07 – 30.15 ± 2.37 0.134 ± 0.011 ↑Antioxidant and anti-inflammatory activities of quercetin [ 102 ] Resveratrol Resveratrol-cyclodextrin complex loaded biodegradable nanoparticles Non-small cell lung cancer 264.2 ± 0.03 2.2±0.4 µ −1.46 ± 1.47 0.16 ± 0.03 ↑Cellular uptake, cytotoxicity, apoptosis, and antioxidant activity [ 103 ] Paclitaxel Reactive Oxygen Species/Glutathione-Responsive Paclitaxel Dimeric nanoparticles Lung cancer 154.8 ± 1.7 – –14.7 ± 0.1 0.111 ± 0.039 ↑Drug release rate [ 104 ] Docetaxel Cholesterol-PEG co-modified poly (n-butyl) cyanoacrylate nanoparticles Lung cancer 182.3 ± 3.2 4.20 ± 0.12 −7.31 ± 0.46 0.217 ± 0.011 ↑The pulmonary absorption time and pass through the air-blood barrier and enter the brain [ 105 ] Naringin PLGA nanoparticles …”

“…Inhaled Qu/CS-NPs ameliorated silica-induced silicosis-associated fibrosis by reducing ROS and malondialdehyde production to attenuate oxidative stress, inhibiting IL-1β and TNF-α release to alleviate inflammation, and downregulating α-smooth muscle actin levels and inhibiting extracellular matrix deposition to improve lung histology. 102 Given the negligible toxicity, inhalation of nanomodified natural products may be a viable therapeutic option for the treatment of silicosis.…”