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Improving the Intracellular Drug Concentration in Lung Cancer Treatment through the Codelivery of Doxorubicin and miR-519c Mediated by Porous PLGA Microparticle
journal contribution
posted on 2016-09-29, 00:00 authored by Di Wu, Chenhui Wang, Jiebing Yang, Hao Wang, Haobo Han, Aijun Zhang, Yan Yang, Quanshun LiPorous
PLGA microparticle for the coencapsulation of doxorubicin and miR-519c
was successfully constructed through the water–oil–water
emulsion solvent evaporation method, using ammonium bicarbonate as
a porogen. It has been characterized with high porous surface, adaptive
aerodynamic diameter (<10 μm), favorable drug loading, and
sustained release profile. The release supernatant exhibited a higher
inhibition of cell proliferation than those from porous PLGA microparticles
harboring a single component (doxorubicin or miR-519c), attributing
to the enhanced induction of cell apoptosis and cell cycle arrest
at S phase. Finally, the improved intracellular concentration of doxorubicin
was elucidated by flow cytometry and liquid chromatography with tandem
mass spectrometry, owing to the knockdown of drug transporter ABCG2
by miR-519c. Overall, the porous PLGA microparticle combining chemotherapy
and gene therapy could facilitate the antitumor efficacy and reduce
the side effects, and thus, it is potential to be used as a sustained
release system for lung cancer treatment via pulmonary administration.