Abstract:
Objective:To construct a drug delivery system of epigallocatechin gallate (EGCG) based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and to study its effect and mechanism on myocardial ischaemic injury.
Methods:The preparation process of EGCG-PLGA nanoparticles (E-P-NPs) was improved, and the morphology of E-P-NPs was observed by transmission electron microscopy. The nanoparticles were characterised by measurement 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 cardiomyocytes 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 myocardial ischemic injury by inhibiting apoptosis and enable EGCG to better exert their efficacy.