Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 12, Issue -, Pages 827-837Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S121948
Keywords
disulfiram; poly(lactic-co-glycolic acid); porous microparticle; non-small-cell lung cancer; antiproliferation; antimigration
Funding
- Natural Science Foundation of China [81373344, 51403074]
- Science and Technology Department of Jilin Province [20140101140JC, 20160520144JH, 20160520146JH]
- Education Department of Jilin Province [2015469]
- Youth Fund of Health and Family Planning Commission of Jilin Province [2013Q026]
- Norman Bethune Program of Jilin University [2015324, 2015423]
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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 mu m), 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-smallcell 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 disulfiramloaded porous PLGA microparticle could achieve favorable antitumor efficiency, implying the potential of treating non-small-cell lung cancer in a pulmonary administration.
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