Platelet membrane-camouflaged nanoparticles carry microRNA inhibitor against myocardial ischaemia‒reperfusion injury.

The incidence of myocardial ischaemia‒reperfusion injury (MIRI) is increasing every year, and there is an urgent need to develop new therapeutic approaches. Nrf2 is thought to play a protective role during MIRI and it is regulated by microRNAs (miRNAs). This study focused on PLGA nanoparticles camouflaged by platelet membrane vesicles (PMVs) (i.e., PMVs@PLGA complexes) carrying microRNA inhibitors, which regulate Nrf2 and can play a therapeutic role in the MIRI process. In vitro and in vivo characterization showed that PMVs@PLGA has excellent transfection efficiency, low toxicity and good targeting. MicroRNAs that effectively regulate Nrf2 were identified, and then PMVs@PLGA-miRNA complexes were prepared and used for in vitro and in vivo treatment. PMVs@PLGA-miRNA complexes can effectively target the delivery of inhibitors to cardiomyocytes. Our results suggest that PMVs@PLGA complexes are a novel delivery system and a novel biological approach to the treatment of MIRI.

Platelet-Membrane-Encapsulated Carvedilol with Improved Targeting Ability for Relieving Myocardial Ischemia-Reperfusion Injury.

In recent years, cell membrane drug delivery systems have received increasing attention. However, drug-loaded membrane delivery systems targeting therapy in myocardial ischemia-reperfusion injury (MIRI) have been relatively rarely studied. The purpose of this study was to explore the protective effect of platelet-membrane-encapsulated Carvedilol on MIRI. We extracted platelets from the blood of adult SD rats and prepared platelet membrane vesicles (PMVs). Carvedilol, a nonselective ß-blocker, was encapsulated into the PMVs. In order to determine the best encapsulation rate and drug-loading rate, three different concentrations of Carvedilol in low, medium, and high amounts were fused to the PMVs in different volume ratios (drugs/PMVs at 2:1, 1:1, 1:2, and 4:1) for determining the optimum concentration and volume ratio. By comparing other delivery methods, including abdominal injection and intravenous administration, the efficacy of PMVs-encapsulated drug-targeted delivery treatment was observed. The PMVs have the ability to target ischemic-damaged myocardial tissue, and the concentration and volume ratio at the optimum encapsulation rate and the drug-loading rate are 0.5 mg and 1:1. We verified that PMVs@Carvedilol had better therapeutic effects compared to other treatment groups, and immunofluorescence observation showed a significant improvement in the apoptosis indicators and infarction area of myocardial cells. Targeted administration of PMVs@Carvedilol may be a promising treatment for myocardial reperfusion injury, as it significantly improves postinjury cardiac function and increases drug utilization compared to other delivery methods.