The effect and mechanism of EGCG-PLGA nanoparticles on alleviating myocardial ischemic injury
Objective:To construct a drug delivery system of epigallocatechin gallate(EGCG)based on poly(lac-tic-co-glycolic acid)(PLGA)nanoparticles,and to study its effect and mechanism on myocardial ischaemic inju-ry.Methods:The preparation process of EGCG-PLGA nanoparticles(E-P-NPs)was improved,and the morpholo-gy of E-P-NPs was observed by transmission electron microscopy.The nanoparticles were characterised by mea-surement of polymer dispersibility index(PDI),zeta potential,nanoparticle size and drug loading rate.The uptake of nanoparticles by cardiomyocytes was observed using fluorescent labelling method.The hypoxia model of car-diomyocytes in vitro and acute myocardial infarction injury model in vivo were established.The effects of EGCG and E-P-NPs with different concentrations on cell viability,level of cardiac troponin I(cTn-I),apoptosis rate as well as levels of Bcl-2,Caspase9 and Bax were detected.Results:The E-P-NPs were spherical in shape,PDI was 0.285,the average particle size was 193.5 nm,the potential was-28.7 mV,and the drug loading rate was 9.23%.The nanoparticles could be taken up by cardiomyocytes.Both in vivo and in vitro experimental studies showed that E-P-NPs dose-dependently could enhance the viability of cardiomyocytes,decrease the level of cTn-I and apoptosis rate,up-regulate the Bcl-2 protein expression,down-regulate the Caspase9 and Bax protein expression,and inhibit the apoptosis.The protective effect of E-P-NPs on ischemic myocardia was better than that of EGCG.Conclusion:E-P-NPs,with concentrated particle size distribution and good homogeneity,can alleviate myocardi-al ischemic injury by inhibiting apoptosis and enable EGCG to better exert their efficacy.