Objective To prepare curcumin loaded monomethoxyl poly(ethylene glycol)-poly(lactic-co-glycolicacid) (mPEG-PLGA) nanopaticles (CUR-NPs), investigate the effect of curcumin (CUR) and CUR-NPs on reversing corticosteroid resistance induced by cigarette smoke extract (CSE), and compare biological function between CUR and CUR-NPs in macrophages RAW264.7. Methods mPEG-PLGA nanoparticles loaded with CUR were prepared via emulsion solvent evaporation.In lipopolysaccharide (LPS) stimulated macrophages RAW264.7, budesonide (BUD) was used to treat macrophages RAW264.7.In LPS and CSE stimulated macrophages RAW264.7, BUD (10^-10-10^-5 mol/L), CUR(10^-10-10^-5 mol/L), CUR(10^-7 mol/L)+BUD(10^-9-10^-5 mol/L), CUR(10^-9-10^-5 mol/L)+BUD(10^-7 mol/L), and CUR-NPs(10^-9-10^-5 mol/L)+BUD(10^-7 mol/L) were respectively used to treat macrophages RAW264.7 activated.The level of IL-8 in cell culture supernatant was measured by ELISA.In CSE stimulated macrophages RAW264.7, CUR(10^-7 and 10^-6 mol/L) and CUR-NPs(10^-7 and 10^-6 mol/L) were used to treat macrophages RAW264.7.The mRNA level of HDAC2 was measured by real-time PCR, the protein level of HDAC2 was measured by Western blot.Cellular uptake of CUR and CUR-NPs in macrophages RAW264.7 was determined by cellular fluorescence intensity observed and detected by laser confocal microscopy imaging. Results The morphology of CUR-NPs was spherical and the mean particle size was (356.4±146.6)nm.Compared with LPS stimulation, co-stimulation of LPS and CSE led to a significant decrease in the maximum inhibitory rate of BUD on IL-8 (P < 0.05) and a significant increase in the 50% inhibitory concentration (IC50) of BUD on IL-8 (P < 0.05).When using LPS+CSE to stimulate, compared with BUD (10^-10-10^-5 mol/L) group, the maximum inhibitory rate of BUD in CUR (10^-7 mol/L)+BUD (10^-9-10^-5 mol/L) group on IL-8 was significantly higher (P < 0.05) and the IC50 of BUD decreased significantly (P < 0.05).When using LPS+CSE to stimulate, CUR and CUR-NPs in 10^-9, 10^-8 and 10^-7 mol/L concentration, the inhibitory rate of CUR-NPs+BUD (10^-7 mol/L) on IL-8 was significantly higher than that of CUR+BUD (10^-7 mol/L) (P < 0.05). CSE stimulation induced a significant decrease in the mRNA and protein expression of HDAC2. Compared with CSE group, the mRNA and protein levels of HDAC2 of CUR(10^-7 and 10^-6 mol/L) group and CUR-NPs(10^-7 and 10^-6 mol/L) group were significantly higher (P < 0.05).In 10^-7 mol/L concentration, the mRNA and protein levels of HDAC2 in CUR-NPs group were significantly higher than those in CUR group.In 10^-7 mol/L concentration, cellular uptake of CUR in CUR-NPs was significantly higher than the native CUR. Conclusions CUR and CUR-NPs can reverse the corticosteroid resistance induced by CSE.CUR-NPs can improve the cellular uptake of CUR.In the case of low concentration, CUR-NPs have more biological activity than CUR.

Citation： WangDi, CuiZhilei, GuoXuejun. The Effect of Curcumin Loaded mPEG-PLGA Nanoparticles on Reversing Corticosteroid Resistance Induced by Cigarette Smoke Extract in Macrophages RAW264.7. Chinese Journal of Respiratory and Critical Care Medicine, 2016, 15(1): 68-74. doi: 10.7507/1671-6205.2016017 Copy