A study reports promising results from a new strategy to target pathological collagen in idiopathic pulmonary fibrosis (IPF) by delivering antifibrotic drugs via penetrating liposomes directly to injured alveoli.
The study, published in the Journal of Control Release, determined that the liposomes were able to deliver pirfenidone and dexamethasone to repair and remodel the lung architecture.
“In this study, dual-drug liposomes co-decorated with collagen-binding peptide and collagenase (COL) could first adhere to the pathological overloaded collagen through the blood circulation, and then the decorated COL could subsequently assist vehicle in penetrating the collagen barrier to efficiently deliver the dual drugs to the damaged fibrotic sites,” the authors explained.
The research team developed a bleomycin-induced IPF mouse model in which to administer the penetrating liposomes containing pirfenidone and dexamethasone. In addition, primary lung fibroblasts and macrophages were treated with the liposomes in vitro in 96-well plates. The authors assessed the antifibrotic activity of the liposomes in vivo in the mouse model and determined the ability of the dual drugs to synergistically heal damaged cells in the in vitro model.
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The results showed that the collagen-binding peptide decorated with the dual drugs helped the liposomes effectively target the pathological collagen in IPF lungs. Furthermore, coating with COL helped the liposomes achieve deep penetration into damaged alveoli, showing the efficacy of the authors’ delivery system.
The team then observed that the dual drugs had a synergistic antifibrotic effect on the pathological collagen, repairing the epithelium and remodeling the extracellular matrix into normal lung architecture.
The authors note that given that pathological collagen accumulation is common in many fibrotic diseases, targeting it with a penetrating carrier of effective antifibrotic drugs could represent an exciting new drug delivery strategy for IPF and other collagen-rich conditions.
Yang MY, Lin YJ, Han, MM, et al. Pathological collagen targeting and penetrating liposomes for idiopathic pulmonary fibrosis therapy. J Control Release. 2022(351):623-637. doi: 10.1016/j.jconrel.2022.09.054