Emerging trends and advances in antioxidant-based plant derived nano formulations in alleviating lung diseases

Chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and lung cancer, are major contributors to global morbidity and mortality. A central driver of their progression is oxidative stress, arising from excessive reactive oxygen species (ROS) that disrupt redox balance, trigger pro-inflammatory cascades, and perpetuate tissue damage. Conventional pharmacological therapies, such as corticosteroids, bronchodilators, and immunosuppressants, provide symptomatic relief but ineffective in addressing oxidative stress and are often limited by adverse effects during long-term use. Plant-derived antioxidants like polyphenols (flavonoid and non-flavonoid) and algae derived antioxidants have demonstrated potent antioxidant and anti-inflammatory effects through direct ROS scavenging, inhibition of NF-κB and MAPK signalling, and activation of Nrf2-dependent cytoprotective pathways. Confirmed in numerous in vitro and in vivo studies, these agents attenuate airway inflammation, oxidative injury, fibrosis, and even carcinogenesis in various respiratory models. Nevertheless, clinical use is still limited due to their poor solubility, instability and low bioavailability. Recent advances in nanotechnology-based delivery systems offer solutions by improving pharmacokinetics, protecting active compounds from degradation, and enabling targeted pulmonary delivery. Preclinical evaluations highlight the enhanced efficacy of nano-formulated phytochemicals in mitigating oxidative stress and inflammation compared with free compounds. This review critically examines the molecular mechanisms of oxidative stress in CRDs, summarises evidence from in vitro and in vivo studies on plant-derived antioxidants, and discusses emerging nano-formulation strategies that optimise their therapeutic potential. Integrating natural antioxidants with nanotechnology holds promise for developing innovative interventions that more effectively disrupt the oxidative–inflammatory cycle underlying CRDs.