Lung inflammation involves the activation of immune cells and inflammatory mediators in response to injury and infection. When inflammation persists, fibroblasts, which are resident lung cells, become activated, leading to pulmonary fibrosis (PF), abnormal wound healing, and long-term damage to the alveolar epithelium. This persistent inflammation and fibrosis can also elevate the risk of lung cancer, emphasizing the need for innovative treatments. Current therapies, such as inhaled corticosteroids (ICS) and chemotherapy, have significant limitations. Although conventional nanoparticles (NPs) provide a promising avenue for treating lung disorders, they have limited selectivity and stability. Polyethylene glycol (PEG) grafting can prevent NP aggregation and phagocytosis, thus prolonging their circulation time. When combined with targeting ligands, PEGylated NPs can deliver drugs precisely to specific cells or tissues. Moreover, pH-sensitive NPs offer the advantage of selective drug delivery to inflammatory or tumor-acidic environments, reducing side effects. These NPs can change their size, shape, or surface charge in response to pH variations, improving drug delivery efficiency. This review examines the techniques of PEGylation, the polymers used in pH-sensitive NPs, and their therapeutic applications for lung inflammation, fibrosis, and cancer. By harnessing innovative NP technologies, researchers can develop effective therapies for respiratory conditions, addressing unmet medical needs and enhancing patient outcomes.
Zerumbone (ZER), a compound derived from the rhizome of Zingiber Zerumbet (L.) Smith, has demonstrated anti-inflammatory properties but suffers from poor water solubility, limiting its clinical application. While ZER's effects on lung inflammation are known, its role in lung fibrosis remains unexplored. Herein, ZER was encapsulated in pH-sensitive liposomes formulated with oleic acid, dipalmitoylphosphatidylcholine, and cholesterol to enhance ZER solubility and delivery to the acidic environment of lung fibrosis. The liposomes were optimized using Box-Behnken design, resulting in an average diameter of 87.8 ± 3.5 nm, a polydispersity index of 0.16 ± 0.2, and a zeta potential of -24 ± 0.32 mV. ZER release from the carrier followed zero-order kinetics and showed higher release in acidic settings. Cascade impactor and HPLC analyses confirmed that ZER liposome powder produced by freeze-drying reached stage 7, indicating effective delivery to deep lung regions. The uptake of ZER liposomes was concentration and pH-dependent, being higher in acidic conditions and greater in MRC-5 cells compared to A549 cells. Notably, ZER liposomes reduced cell migration and downregulated fibrotic markers such as fibronectin, MMP-2, and α-SMA in MRC-5 and A549 cells. This study suggests that ZER liposomes hold promise for treating lung fibrosis and merit further investigation.
Lung cancer is the leading cause of cancer-associated mortality and non-small cell lung carcinoma (NSCLC) constitutes 85 % of all lung cancer cases. This malignancy is characterized by multifactorial risk factors, poor prognosis, and deplorable clinical outcome. Considerable evidence indicates that there is inter-individual variability in the lung cancer predisposition and survival due to genetic variations introduced by genetic polymorphisms between individuals, indirectly affecting the lung cancer susceptibility and the patient survival. In the past decades, immune landscape in the tumour environment and host immune response are constantly implicated as determining factor in NSCLC development and patients' survival. With the change of paradigm in NSCLC treatment to immunotherapy and increasing recognition of the role of the immune system in cancer development and survival, the inspection of single nucleotide polymorphisms (SNPs) in immunomodulated markers associated with the risk and prognosis for NSCLC is crucial. Despite extensive studies reported the implication of SNPs in predicting the risk and survival of NSCLC. SNPs in the genes that modulate immune response in NSCLC have not been reviewed before. Hence, this review uncovers the evidence on the genetic polymorphisms of immunomodulatory markers which include immune checkpoints, immune checkpoint inhibitors, chemokines, interleukins, human leukocyte antigen and its receptors, and antigen presenting machinery genes, and their significance in the susceptibility, prognosis and survival in NSCLC. The identification of genetic factors associated with NSCLC risk and survival provides invaluable information for a greater comprehension of the pathogenesis and progression of the disease, also to refine prognosis and personalize clinical care in early and advanced-stages disease.