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

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 Engin...

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Autores principales: Wang C, Yang J, Han H, Chen J, Wang Y, Li Q
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Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:8779a7908380464d919d77fe5602228b2021-12-02T01:34:50ZDisulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer1178-2013https://doaj.org/article/8779a7908380464d919d77fe5602228b2017-01-01T00:00:00Zhttps://www.dovepress.com/disulfiram-loaded-porous-plga-microparticle-for-inhibiting-the-prolife-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Chenhui 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, antimigrationWang CYang JHan HChen JWang YLi QWang YDove Medical PressarticleDisulfiramPoly(lactic-co-glycolic acid)Porous microparticleNon-small cell lung cancerAnti-proliferationAnti-migrationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 827-837 (2017)
institution DOAJ
collection DOAJ
language EN
topic Disulfiram
Poly(lactic-co-glycolic acid)
Porous microparticle
Non-small cell lung cancer
Anti-proliferation
Anti-migration
Medicine (General)
R5-920
spellingShingle Disulfiram
Poly(lactic-co-glycolic acid)
Porous microparticle
Non-small cell lung cancer
Anti-proliferation
Anti-migration
Medicine (General)
R5-920
Wang C
Yang J
Han H
Chen J
Wang Y
Li Q
Wang Y
Disulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer
description 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
format article
author Wang C
Yang J
Han H
Chen J
Wang Y
Li Q
Wang Y
author_facet Wang C
Yang J
Han H
Chen J
Wang Y
Li Q
Wang Y
author_sort Wang C
title Disulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer
title_short Disulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer
title_full Disulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer
title_fullStr Disulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer
title_full_unstemmed Disulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer
title_sort disulfiram-loaded porous plga microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/8779a7908380464d919d77fe5602228b
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