Abstract
This report describes the development of polyplexes based on CXCR4-inhibiting poly(ethylenimine) derivative (PEI-C) for pulmonary delivery of siRNA to silence plasminogen activator inhibitor-1 (siPAI-1) as a new combination treatment of pulmonary fibrosis (PF). Safety and delivery efficacy of the PEI-C/siPAI-1 polyplexes was investigated in vitro in primary lung fibroblasts isolated from mice with bleomycin-induced PF. Biodistribution analysis following intratracheal administration of fluorescently labeled polyplexes showed prolonged retention in the lungs. Treatment of mice with bleomycin-induced PF using the PEI-C/siPAI-1 polyplexes resulted in a significant down-regulation of the PAI-1 expression and decreased collagen deposition in the lung. The results of this study provide first evidence of the potential benefits of combined inhibition of CXCR4 and PAI-1 in the pulmonary treatment of PF.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1765-1776 |
| Number of pages | 12 |
| Journal | Nanomedicine: Nanotechnology, Biology, and Medicine |
| Volume | 14 |
| Issue number | 6 |
| DOIs | |
| State | Published - Aug 2018 |
Keywords
- CXCR4
- Intratracheal administration
- PAI-1
- Pulmonary fibrosis
- siRNA
ASJC Scopus subject areas
- Bioengineering
- Medicine (miscellaneous)
- Molecular Medicine
- Biomedical Engineering
- General Materials Science
- Pharmaceutical Science