Tetrahedral Framework Nucleic Acids Delivery of Pirfenidone for Anti-Inflammatory and Antioxidative Effects to Treat Idiopathic Pulmonary Fibrosis.
Yuting XieSirong ShiWeitong LvXinyu WangLin YueConghui DengDoudou WangJing HanTinghong YeYunfeng LinPublished in: ACS nano (2024)
Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible lung disease, and developing an effective treatment remains a challenge. The limited therapeutic options are primarily delivered by the oral route, among which pirfenidone (PFD) improves pulmonary dysfunction and patient quality of life. However, its high dose and severe side effects (dyspepsia and systemic photosensitivity) limit its clinical value. Intratracheal aerosolization is an excellent alternative method for treating lung diseases because it increases the concentration of the drug needed to reach the focal site. Tetrahedral framework nucleic acid (tFNA) is a drug delivery system with exceptional delivery capabilities. Therefore, we synthesized a PFD-tFNA (Pt) complex using tFNA as the delivery vehicle and achieved quantitative nebulized drug delivery to the lungs via micronebulizer for lung fibrosis treatment. In vivo , Pt exhibited excellent immunomodulatory capacity and antioxidant effects. Furthermore, Pt reduced mortality, gradually restored body weight and improved lung tissue structure. Similarly, Pt also exhibited superior fibrosis inhibition in an in vitro fibrosis model, as shown by the suppression of excessive fibroblast activation and epithelial-mesenchymal transition (EMT) in epithelial cells exposed to TGF-β1. Conclusively, Pt, a complex with tFNA as a transport system, could enrich the therapeutic regimen for IPF via intratracheal aerosolization inhalation.
Keyphrases
- idiopathic pulmonary fibrosis
- epithelial mesenchymal transition
- anti inflammatory
- interstitial lung disease
- body weight
- drug delivery
- high dose
- nucleic acid
- transforming growth factor
- oxidative stress
- low dose
- pulmonary hypertension
- risk factors
- high resolution
- rheumatoid arthritis
- cardiovascular events
- type diabetes
- signaling pathway
- stem cell transplantation
- combination therapy
- physical activity
- case report
- body mass index
- systemic sclerosis
- replacement therapy
- coronary artery disease
- weight gain
- helicobacter pylori
- smoking cessation