Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment

• Published in: Pharmaceutics Vol. 12; no. 3; p. 206
• Main Authors: Parvathaneni, Vineela, Kulkarni, Nishant S, Shukla, Snehal K, Farrales, Pamela T, Kunda, Nitesh K, Muth, Aaron, Gupta, Vivek
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 28.02.2020; MDPI AG
• Subjects: 3d spheroid; apoptosis; liposomes; non-small cell lung cancer; pirfenidone; repurposing; non-small cell lung cancer; apoptosis; repurposing; 3D spheroid; liposomes; pirfenidone
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics12030206

Non-small cell lung cancer (NSCLC) is a global disorder, treatment options for which remain limited with resistance development by cancer cells and off-target events being major roadblocks for current therapies. The discovery of new drug molecules remains time-consuming, expensive, and prone to failure in safety/efficacy studies. Drug repurposing (i.e., investigating FDA-approved drug molecules for use against new indications) provides an opportunity to shorten the drug development cycle. In this project, we propose to repurpose pirfenidone (PFD), an anti-fibrotic drug, for NSCLC treatment by encapsulation in a cationic liposomal carrier. Liposomal formulations were optimized and evaluated for their physicochemical properties, in-vitro aerosol deposition behavior, cellular internalization capability, and therapeutic potential against NSCLC cell lines in-vitro and ex-vivo. Anti-cancer activity of PFD-loaded liposomes and molecular mechanistic efficacy was determined through colony formation (1.5- to 2-fold reduction in colony growth compared to PFD treatment in H4006, A549 cell lines, respectively), cell migration, apoptosis and angiogenesis assays. Ex-vivo studies using 3D tumor spheroid models revealed superior efficacy of PFD-loaded liposomes against NSCLC, as compared to plain PFD. Hence, the potential of inhalable liposome-loaded pirfenidone in NSCLC treatment has been established in-vitro and ex-vivo, where further studies are required to determine their efficacy through in vivo preclinical studies followed by clinical studies.