Pulmonary delivery of polyplexes for combined PAI-1 gene silencing and CXCR4 inhibition to treat lung fibrosis

Pulmonary fibrosis (PF) is a chronic inflammatory fibrotic disorder with limited therapeutic approaches. If left untreated, PF progresses into a fatal disease within several years of medical diagnosis. Here, we report development of novel combination nanomedicine pulmonary treatment based on inhibition of PAI-1 and CXCR4 - two relevant targets in the pathophysiology of PF. The developed nanomedicines are based on CXCR4-inhibiting polymer (PEI-C22) that delivers siRNA to silence PAI-1 expression in fibrotic lungs.149