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Disulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer

Authors Wang C, Yang J, Han H, Chen J, Wang Y, Li Q, Wang Y

Received 9 September 2016

Accepted for publication 20 December 2016

Published 24 January 2017 Volume 2017:12 Pages 827—837

DOI https://doi.org/10.2147/IJN.S121948

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Linlin Sun


Chenhui Wang,1,2,* Jiebing Yang,1,3,* Haobo Han,3 Jiawen Chen,3 Yudi Wang,3 Quanshun Li,3 Yanbo Wang1

1Department of Urology, First Hospital of Jilin University, 2Innovative Drug Research Centre, School of Pharmacy, Chongqing University, Chongqing, 3Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People’s Republic of China

*These authors contributed equally to this work

Abstract: In this study, poly(lactic-co-glycolic acid) (PLGA) was used as a carrier to construct disulfiram-loaded porous microparticle through the emulsion solvent evaporation method, using ammonium bicarbonate as a porogen. The microparticle possessed highly porous surface, suitable aerodynamic diameter for inhalation (8.31±1.33 µm), favorable drug loading (4.09%±0.11%), and sustained release profile. The antiproliferation effect of release supernatant was detected through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay using non-small-cell lung cancer A549 as a model, with only 13.3% of cell viability observed for the release supernatant at 7 days. The antiproliferation mechanism was elucidated to be associated with the enhanced induction of cell apoptosis and cell cycle arrest at S phase through flow cytometry and Western blotting analysis. Finally, wound healing and transwell migration assay showed that they could efficiently inhibit the cell migration. These results demonstrated that disulfiram-loaded porous PLGA microparticle could achieve favorable antitumor efficiency, implying the potential of treating non-small-cell lung cancer in a pulmonary administration.

Keywords: disulfiram, poly(lactic-co-glycolic acid), porous microparticle, non-small-cell lung cancer, antiproliferation, antimigration

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