Development and Evaluation of a Novel Inhalable Liposomal Powder Co-Encapsulating ASSNAC and Pirfenidone via Spray Freeze-Drying for Targeted Pulmonary Fibrosis Therapy
Preclinical study demonstrates that inhaled liposomal ASSNAC and pirfenidone reduces lung injury in rat fibrosis models, suggesting a potent therapy that circumvents oral drug toxicity.
Key Points
Develop an inhalable dry powder co-encapsulating ASSNAC and pirfenidone in liposomes via spray freeze-drying to improve pulmonary drug delivery and reduce systemic toxicities in pulmonary fibrosis.
Formulated liposomal dry powders co-encapsulating ASSNAC and pirfenidone using spray freeze-drying with L-leucine as a cryoprotectant and particle surface modifier.
Evaluated aerodynamic characteristics, safety, and anti-fibrotic efficacy in TGF-β1-stimulated Beas-2B and HFL-1 cells.
Tested therapeutic outcomes, histological lung injury, collagen levels, and TGF-β1 signaling pathways in bleomycin-induced pulmonary fibrosis rats.
Spray freeze-dried powders exhibited a fine particle fraction of 61.08% ± 2.45% and a mass median aerodynamic diameter of 2.22 ± 0.11 µm, with cell viability > 90% and negligible hemolysis.
In vitro dual-treatment preserved epithelial cell morphology, enhanced wound closure, suppressed fibroblast invasion, and lowered Collagen I, Collagen III, and α-SMA expression.
In pulmonary fibrosis rats, inhaled powder attenuated lung injury, restored redox balance, decreased hydroxyproline, and suppressed TGF-β1 and Collagen III accumulation.