Biodegradable Polymeric Based Nanoparticles for Atherosclerosis and Myocardial Infarction Targeting Potentials and Future

INTRODUCTION

There are an expectations that there will be an increase in the mortality rate that is a attributed to the cardiovascular disorders within the period from 2025 to 2050, and atherosclerosis diseases will take the major share of this rate,^[1] and it is important to have a brief description of pathophysiology of the different types of the heart disorders to be able to design the appropriate prophylactic or remedial therapeutic systems.

Atherosclerosis is a continuous process where the artery wall lesions are made by means of lipids accumulation inducing a localized modification that is developed to a chronic inflammation that ends up to complex situation known as atherosclerosis. The most critical issue in this pathophysiology is the formation of fibrous plaque lesions that are able to rupture at any time inducing arterial clogging.^[2]

On the other hand, myocardial infarction is an acute occlusion in one of the of the large epicardial coronary arteries with a duration of about 20–40 min which originates from a plaque rupture that is formed in the coronary arteries and normally will lead to oxygen deficiency which consequently leads to myocardium followed by histological transformation in addition to mitochondrial alterations and finally liquefactive necrosis of myocardial tissue, and the lack of tissue regeneration at this stage is attributed to the heart remodeling into dilation, segmental hypertrophy of the other normal tissue.^[3]

New natural/synthetic composites nano-structures have been designed to be used in cardiovascular tissue regeneration owing to its unique physicochemical properties,^[4] basically these structures should have biocompatibility with the and have a certain physical characteristics that make it able to comply with the normal myocardium cells,^[5] in addition to the specific characteristics of these carriers represented by low cost, flexibility, stability, low side adverse reactions and toxicity, active ingredient entrapment capabilities, and above all the sustained and programmed drug release kinetics,^[6] [Figure 1].^[7] Cell surface glycoprotein (C44), which is a multi-faceted receptor and strongly correlates to the initiation and progression of atherosclerosis by inflammatory response, promotes the thing which makes it a good candidate for targeted treatment.^[8]

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Figure 1:

Nanoparticles mode of action in atherosclerosis.

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DISCUSSION

Data and thoughts were extracted and arranged in such a way as to direct the research toward generating more innovative ideas.

Ma et al., in a study (in mice) developed a new approach for active targeting of Atherosclerosis plaques with nano-agent used as imaging and therapeutic agents carrier so that Rosuvastatin loaded hyaluronic acid-guided cerasome nano-formulation was used to target cluster of differentiation 44 receptors in the arterial plaque region and the results revealed a considerable reduce in plaque in comparison to as the free drug alone.^[9] Furthermore, Bartusik-Aebisher et al. reported that inflammation development can be eliminated by nanoparticles loaded with active ingredients such as small interfering RNA (siRNA), microRNA (miRNA), or other protein biomolecules that inhibit macrophage signaling pathways, which play a crucial role in Atherosclerosis development.^[10] Zhao et al. reported also that a well-designed multifunctional double wall nanoparticles composed of poly(lactic-co-glycolic acid) (PLGA) loaded with atorvastatine/siRNA nanoparticles revealed a good efficiency against atherosclerosis represented a magnificent reduction in plaque, coupled with decrease in lipid accumulation, in addition to a reduction in CD68+ macrophage content and also a decrease in monocyte chemoattractant protein 1 content.^[11] Leal et al. also reported that miRNA-124a and atorvastatin-loaded PLGA, a poly nanoparticle can combat atherosclerosis, so that this combined therapy dramatically decreased the proinflammatory cytokines as tumor necrosis factor alpha, reactive oxygen, and interleukin-6 in the promoted macrophages and arterial cells. In addition to low-density lipoproteins accumulation prevention inside macrophages in comparison with the case where only one active ingredient is loaded nanoparticles.^[12]

Jiang et al., revealed that atorvastatin, siRNA loaded in modified galactose-modified trimethyl chitosan nanoparticles, were able to induce anti-inflammatory and lipid regulation effects on mice with atherosclerosis, either in the intravenous or the oral route.^[13] more over Wang et al., reported that atherosclerosis can be treated by targeting Liver X receptors receptor in atherosclerotic macrophages, so that the stimulation of this receptor using high-density lipoprotein-loaded cyclodextrin nanoparticles the thing that leads to the regulation of cholesterol efflux and efferocytosis. This targeting system revealed that after several months of treatment with hyaluronan-targeted reconstituted high-density lipoprotein nanoplatform, there was a noticeable plaque amount reduction and lipid accumulation elimination.^[14]

Liu et al. reported that VX765 (selective caspase-1) inhibitor that is coated polyethyleneimine/sodium alginate composite nano gels were able to induce a noticeable enhancement of the cardiac function, reduced of the infarct size, fibrosis, and apoptosis in rats with myocardial infarction,^[15] also Chang et al. found that that one dose intra-myocardial injection of PLGA insulin-like growth factor nanoparticles was able to prevent cardiomyocyte apoptosis in addition to a reduction of the infarct size, furthermore there was an improve in left ventricle ejection fraction for 21 in mice with myocardial infarction.^[16]

Jin Zhou reported that melanin nL/alginate hydrogels revealed regenerative effect in rats with myocardial infarction due to anti-oxidation and macrophage polarization effects that regulate the myocardial infarction micro-environment by converting macrophages to M2 macrophage.^[17]

Tapeinos et al. reported that PLGA microspheres coated with collagen and anchored with MnO₂ were able to clear the excess reactive oxygen is overexposed in cardiovascular disorders and to control the apoptosis of oxidative stress undergoing cells that is mediated by H₂O₂.^[18] Ikeda et al. reported that polylactic/glycolic acid nanoparticles, loaded with cyclosporine A, inhibited the mitochondrial permeability-transition pores, and pitavastatin reduced inflammatory and oxidative stress in addition to leukocyte–endothelial interactions, which are considered key factors in ischemia–reperfusion injury, significantly supported the cardioprotection during the acute phase of myocardial ischemia–reperfusion injury in comparison with the administration of either cyclosporine A or pitavastatin loaded alone with the same carrier.^[19]

Garbayo et al. reported a study that PLGA micro-particles coated with biomimetic materials (collagen type 1) and polyD-lysine, and attached with cardiac progenitor cells (heart regenerative stem cells). This coated micro-particle-based system, when implanted within the infarcted myocardial micro-environment in rats, was able to improve the therapeutic ability of cardiac progenitor cells and to increase the heart’s functional recovery in a prolonged manner in comparison with the treatment with cardiac progenitor cells alone.^[20] Atherosclerosis and myocardial infarction are driven by a convergence of atherogenic dyslipidemia, visceral adiposity, and population-specific metabolic risk, which accelerate plaque formation and instability.^[21] The distinctive lipid patterns (high triglycerides, dysfunctional HDL, and elevated atherogenic particles) described highlight mechanisms predisposing to premature coronary plaque rupture and MI, especially in high-risk groups.^[22] Looking ahead, these findings support future strategies targeting early, ethnicity-tailored lipid modulation and obesity-linked metabolic pathways to prevent atherosclerosis progression and acute myocardial infarction.^[23] Furthermore, Ghaziof et al. reported that electrically conductive and 3-D nano-composite poly-caprolactone/gold carriers can be used as a scaffold for myocardium regeneration.^[24]

CONCLUSION

It is clear that biodegradable polymeric-based nanoparticles are good candidate for targeting some critical cardiovascular system diseases, such as a atherosclerosis, myocardial infarction, in addition to the ability to be used in tissue generation and helping the heart restore functionality, and the combination of more than on approach for cardiovascular system targeting may give a chance for more precise therapeutic outcomes.