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.

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

“…In previous studies, we verified that PMVs are well targeted to the site of injury in the heart as carriers in the treatment of MIRI [ 32 ]. Here, we used DiR to label PMVs and PLGA and assembled them into PMVs@PLGA complexes, validating their targeting in MIRI rats (using an equal volume of PBS as NC).…”

Cell or cell derivative-laden hydrogels for myocardial infarction therapy: from the perspective of cell types

“…219 In addition, researchers have delivered non-selective b-blockers (Carvedilol), tissue fibrinogen activator (tPA), and CSCs-derived secretome by platelet membrane-coated nanoparticles for treating MI. 220 5.2.2 Stem/progenitor cell membrane-camouflaged nanoparticles. Similar to blood cells, stem cells show certain immune escape ability.…”

“…219 In addition, researchers have delivered non-selective β-blockers (Carvedilol), tissue fibrinogen activator (tPA), and CSCs-derived secretome by platelet membrane-coated nanoparticles for treating MI. 220…”

Platelet-inspired targeting delivery for coronary heart disease

“… i.v. 14.9-fold higher concentrations in the infarcted area compared with bare nanocells 3.4- and 8.6-fold higher concentrations in the heart than in the liver and kidney respectively Increased accumulation in I/R regions Increased circulation time than EVs Increased targeting ability to monocytes/macrophages/injured endothelial cells ↑Cardiac function ↑Neovascularization ↑Cardiomyocytes proliferation ↑Activation of endogenous stem/progenitor cells ↓Heart remodeling ↑Cardiac function ↓Myocardial cell apoptosis ↑Cardiac function ↓Inflammatory response ↑Cardiac function ↓Heart remodeling ↑Neovascularization [ 45 ] [ 46 ] [ 49 , 51 ] Resolvin D1 Circulating EVs Mouse Mouse i.v. i.v.…”

“…Systematically administered PINCs are shown with higher concentrations in the infarcted heart than in the liver or kidney, thus resulting in improved cardiac function and mitigated ventricular remodeling in the mice with ischemia-reperfusion (I/R) injury. Besides, Zhou et al [ 46 ] also demonstrate the targeting ischemic-damaged myocardial tissue ability and the protective postinjury cardiac function of platelet-membrane-encapsulated Carvedilol. Extracellular vesicles are considered to be intercellular communication carriers [ 47 ].…”