Development of inhalable quinacrine loaded bovine serum albumin modified cationic nanoparticles: Repurposing quinacrine for lung cancer therapeutics

Research output: Contribution to journalArticle

Authors

  • Bhuvaneshwar Vaidya
  • Nishant S. Kulkarni
  • Snehal K. Shukla
  • Vineela Parvathaneni
  • Gautam Chauhan
  • Jenna K. Damon
  • Apoorva Sarode
  • Jerome V. Garcia
  • Nitesh Kunda
  • Samir Mitragotri
  • Vivek Gupta

External Institution(s)

  • Keck Graduate Institute
  • St. John's University
  • University of La Verne
  • Harvard University

Details

Original languageEnglish (US)
Article number118995
JournalInternational Journal of Pharmaceutics
Volume577
StatusPublished - Mar 15 2020
Peer-reviewedYes

Abstract

Drug repurposing is on the rise as an atypical strategy for discovery of new molecules, involving use of pre-existing molecules for a different therapeutic application than the approved indication. Using this strategy, the current study aims to leverage effects of quinacrine (QA), a well-known anti-malarial drug, for treatment of non-small cell lung cancer (NSCLC). For respiratory diseases, designing a QA loaded inhalable delivery system has multiple advantages over invasive delivery. QA-loaded nanoparticles (NPs) were thus prepared using polyethyleneimine (PEI) as a cationic stabilizer. While the use of PEI provided cationic charge on the particles, it also mediated a burst release of QA and demonstrated potential particle toxicity. These concerns were circumvented by coating nanoparticles with bovine serum albumin (BSA), which retained the cationic charge, reduced NP toxicity and modulated QA release. Prepared nanoparticles were characterized for physicochemical properties along with their aerosolization potential. Therapeutic efficacy of the formulations was tested in different NSCLC cells. Mechanism of higher anti-proliferation was evaluated by studying cell cycle profile, apoptosis and molecular markers involved in the progression of lung cancer. BSA coated QA nanoparticles demonstrated good aerosolization potential with a mass median aerodynamic diameter of significantly less than 5 µm. Nanoparticles also demonstrated improved therapeutic efficacy against NSCLC cells in terms of low IC50 values, cell cycle arrest at G2/M phase and autophagy inhibition leading to increased apoptosis. BSA coated QA NPs also demonstrated enhanced therapeutic efficacy in a 3D cell culture model. The present study thus lays solid groundwork for pre-clinical and eventual clinical studies as a standalone therapy and in combination with existing chemotherapeutics.

    Research areas

  • Aerosolization, Apoptosis, Autophagy, Cationic nanoparticles, Non-small cell lung cancer, Quinacrine

Citation formats

APA

Vaidya, B., Kulkarni, N. S., Shukla, S. K., Parvathaneni, V., Chauhan, G., Damon, J. K., ... Gupta, V. (2020). Development of inhalable quinacrine loaded bovine serum albumin modified cationic nanoparticles: Repurposing quinacrine for lung cancer therapeutics. International Journal of Pharmaceutics, 577, [118995]. https://doi.org/10.1016/j.ijpharm.2019.118995

Harvard

Vaidya, B, Kulkarni, NS, Shukla, SK, Parvathaneni, V, Chauhan, G, Damon, JK, Sarode, A, Garcia, JV, Kunda, N, Mitragotri, S & Gupta, V 2020, 'Development of inhalable quinacrine loaded bovine serum albumin modified cationic nanoparticles: Repurposing quinacrine for lung cancer therapeutics', International Journal of Pharmaceutics, vol. 577, 118995. https://doi.org/10.1016/j.ijpharm.2019.118995