Improving the Intracellular Drug Concentration in Lung Cancer Treatment through the Codelivery of Doxorubicin and miR-519c Mediated by Porous PLGA Microparticle.

Abstract

Porous 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.