Pulmonary delivery of gene-loaded lipid nanoparticles for targeting TGF-β signaling in idiopathic pulmonary fibrosis

Idiopathic Pulmonary Fibrosis (IPF) is chronic, progressive interstitial lung disease characterized by the accumulation of extracellular matrix (ECM) and remodeling of lung tissue. The existing antifibrotic therapies offer limited disease modification, underscoring the need for targeted and precise treatment strategies. Advances in LNP platforms, including solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) and liposomes, are studied for their ability to encapsulate and deliver nucleic acid therapies such as Small interfering RNA (siRNA), microRNA (miRNA) and CRISPR/Cas9 directly to the lungs. This review addresses a key gap by critically evaluating inhalable lipid nanoparticle (LNP) platforms for gene modulation of transforming growth factor-β (TGF-β) signaling in IPF. Additionally, LNP-mediated delivery of CRISPR components enables durable gene editing with minimal systemic toxicity. Overall, inhalable gene-loaded LNPs represent a promising direction for disease-modifying therapy in IPF, provided that delivery efficiency, safety, and regulatory challenges are systematically addressed.