Curcumin-loaded PEG-PDLLA nanoparticles for attenuating palmitate-induced oxidative stress and cardiomyocyte apoptosis through AMPK pathway

Curcumin (CUR) has the ability to attenuate oxidative stress in the myocardium and to protect the myocardium from lipotoxic injury owing to its lipid-reducing properties. However, the use of CUR is limited due to its hydrophobicity and instability. In this study, CUR-loaded nanoparticles (CUR NPs) were developed using an amphiphilic copolymer, monomethoxy poly (ethylene glycol)-b-poly (DL-lactide), as a vehicle material. CUR NPs with high drug loading and small size were prepared under optimized conditions. The effects of CUR NPs on palmitate-induced cardiomyocyte injury were investigated and the possible protective mechanism of CUR NPs was also examined. It was found that CUR NPs were able to control the release of CUR and to deliver CUR to H9C2 cells, and they could prevent palmitate-treated H9C2 cells from apoptosis. In addition, CUR NPs could regulate the Bax and Bcl-2 levels of palmitate-treated H9C2 cells back to their respective normal levels. A prospective mechanism for the function of CUR NPs is that they may activate the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin complex-1/p-p70 ribosomal protein S6 kinase signaling pathway, regulate the expression of downstream proteins and resist the palmitate-induced cardiomyocyte injury. Results suggest that CUR NPs can attenuate palmitate-induced oxidative stress in cardiomyocytes and protect cardiomyocytes from apoptosis through the AMPK pathway. In view of the safety and efficiency of these CUR NPs, they have potential for application in protecting the myocardium from lipotoxic injury.