Nanocarriers for lung health: ameliorating inflammation and cell aging using flavonoid-based nano nutrients

Chronic respiratory diseases (CRDs) affect over 545 million individuals globally, with COPD alone causing approximately 3.2 million deaths annually. Flavonoids have shown promise in reducing lung inflammation and disease risk; however, their clinical application is hindered by poor solubility and low bioavailability. Nanocarrier-based pulmonary delivery systems offer a solution by enabling targeted, controlled release and improved solubility.

This review explores the preclinical and clinical potential of flavonoid-loaded nanocarriers in mitigating CRDs by regulating inflammation and cellular senescence, while offering sustained release and enhanced biocompatibility.

A comprehensive analysis of flavonoid mechanisms in modulating inflammatory pathways (e.g. NF-κB, Nrf2/Keap1) and enzymes (COX, 5-LOX, iNOS) was conducted using data from electronic databases (PubMed, ScienceDirect, Web of Science, TRIP, Springer). MeSH terms included 'Flavonoids,' 'Preclinical Studies,' 'Clinical Trials,' and 'Lung Health.' Taxonomy, epidemiology, and chemical data were verified using World Flora Online, WHO factsheets, and ChemSpider.

Flavonoid-loaded nanocarriers demonstrated significant anti-inflammatory and antioxidant effects. PLGA-based systems reduced TNF-α and IL-6 levels by up to 80%. Lipid-based carriers (SLNs, NLCs) enhanced bioavailability 2-5 fold, while liposomes improved cell viability (40-50%) and reduced oxidative stress (>60%). Inhalable nanoformulations, such as quercetin achieved 3-fold higher lung concentration and 50% longer retention compared with oral formulations.

Flavonoid-loaded nanocarriers, especially liposomes, show enhanced pulmonary targeting, bioavailability, and therapeutic efficacy in CRDs. Their ability to suppress inflammation and cellular aging highlights their potential as a promising nanomedicine strategy for improving lung health.