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

Abstract

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 β-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.