Systematic development and optimization of inhalable pirfenidone liposomes for non-small cell lung cancer treatment

Research output: Contribution to journalArticle

Authors

  • Vineela Parvathaneni
  • Nishant S. Kulkarni
  • Snehal K. Shukla
  • Pamela T. Farrales
  • Nitesh K. Kunda
  • Aaron Muth
  • Vivek Gupta

External Institution(s)

  • St. John's University

Details

Original languageEnglish (US)
Article number206
JournalPharmaceutics
Volume12
Issue number3
StatusPublished - Mar 2020
Peer-reviewedYes

Abstract

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.

    Research areas

  • 3D spheroid, Apoptosis, Liposomes, Non-small cell lung cancer, Pirfenidone, Repurposing

Citation formats

APA

Parvathaneni, V., Kulkarni, N. S., Shukla, S. K., Farrales, P. T., Kunda, N. K., Muth, A., & Gupta, V. (2020). Systematic development and optimization of inhalable pirfenidone liposomes for non-small cell lung cancer treatment. Pharmaceutics, 12(3), [206]. https://doi.org/10.3390/pharmaceutics12030206

Harvard

Parvathaneni, V, Kulkarni, NS, Shukla, SK, Farrales, PT, Kunda, NK, Muth, A & Gupta, V 2020, 'Systematic development and optimization of inhalable pirfenidone liposomes for non-small cell lung cancer treatment', Pharmaceutics, vol. 12, no. 3, 206. https://doi.org/10.3390/pharmaceutics12030206