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Open AccessArticle

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

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11439, USA
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Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(3), 206; https://doi.org/10.3390/pharmaceutics12030206
Received: 24 January 2020 / Revised: 24 February 2020 / Accepted: 25 February 2020 / Published: 28 February 2020
(This article belongs to the Special Issue Advances in Pulmonary Drug Delivery)
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. View Full-Text
Keywords: repurposing; non-small cell lung cancer; pirfenidone; liposomes; 3D spheroid; apoptosis repurposing; non-small cell lung cancer; pirfenidone; liposomes; 3D spheroid; apoptosis
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MDPI and ACS Style

Parvathaneni, V.; Kulkarni, N.S.; Shukla, S.K.; Farrales, P.T.; Kunda, N.K.; Muth, A.; Gupta, V. Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment. Pharmaceutics 2020, 12, 206. https://doi.org/10.3390/pharmaceutics12030206

AMA Style

Parvathaneni V, Kulkarni NS, Shukla SK, Farrales PT, Kunda NK, Muth A, Gupta V. Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment. Pharmaceutics. 2020; 12(3):206. https://doi.org/10.3390/pharmaceutics12030206

Chicago/Turabian Style

Parvathaneni, Vineela; Kulkarni, Nishant S.; Shukla, Snehal K.; Farrales, Pamela T.; Kunda, Nitesh K.; Muth, Aaron; Gupta, Vivek. 2020. "Systematic Development and Optimization of Inhalable Pirfenidone Liposomes for Non-Small Cell Lung Cancer Treatment" Pharmaceutics 12, no. 3: 206. https://doi.org/10.3390/pharmaceutics12030206

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