Heart diseases together with circulatory diseases known as cardiovascular diseases maintain their position as the world’s leading cause of mortality because these disorders killed about 33% of people during 2021. Medical progress and diagnostic innovation have not addressed the major obstacles within current therapeutic approaches, which involve systemic toxicity together with non-specific drug distribution and invasive medical interventions. The field of nanotechnology delivers beneficial solutions through its capacity to direct medications, along with managing their release mechanisms and improving visualization precision. Therapeutic efficacy gets enhanced with diminished side effects through the application of nanoparticle (NP)-based systems, including polymeric NPs, liposomes, dendrimers, and solid lipid NPs. The field of molecular imaging and regenerative cardiology has experienced advancements through the implementation of novel nanomaterials, including gold NPs, carbon nanotubes, and graphene derivatives. This analysis examines current developments in nanomedicine, which supports cardiovascular disease diagnostics and therapy while demonstrating its ability to revolutionize precise cardiology practices through specific treatments, along with minimally invasive tests and integrated therapeutic systems.
Cardiovascular diseases (CVDs) are disorders related to the heart, valvular, blood vessels, and the circulatory system. As cardiovascular system functions for the normal blood circulation, any error related to this system can cause hypertension, atherosclerosis, heart failure, ischemic heart diseases, stroke, angina pectoris, aorta disease, peripheral vascular disease, myocardial infarction (MI), and congestive heart failure etc. Heart diseases together with blood vessel disorders comprise CVDs which show different origins alongside several risk factors. The combination of high cholesterol with hypertension and smoking, combined with diabetes and obesity, causes atherosclerosis which leads to Coronary Artery Disease then produces myocardial ischemia that may evolve to infarction. Extended exposure to hypertension causes left ventricular hypertrophy, arrhythmias, and heart failure through hypertensive heart disease development. Heart failure occurs because of Coronary Artery Disease, hypertension, cardiomyopathy, or valvular disorders, thus reducing the blood circulation capacity in the heart. The presence of cardiomyopathies arises due to genetic origins or infections, alcohol abuse, or disorders that weaken heart muscles and raise the probability of heart failure. Providing early diagnosis requires comprehensive knowledge about the conditions and their root causes alongside the necessary treatment strategies and prevention methods.
CVDs are considered to be the deadliest disorders. According to World Health Organization, CVDs are responsible for the deaths of 20.5 million people, that is,33% of all the global deaths in 2021. It is estimated that in 2030, the death rate due to CVDs could be raised up to 25 million. In 2018, 20.28% of total deaths, that is, 251,200 deaths were caused by CVDs, in Pakistan. According to the 2019 Global Burden of Disease study, Pakistan had an age-standardized CVD death rate of 357.88 per 100,000 individuals, which was higher than the global rate of 239.85 per 100,000 ahajournals org . Given the global trend of increasing CVD cases and deaths from 34.74 million cases and 12.33 million deaths in 1990 to 66.81 million cases and 20.5 million deaths in 2021 pmc ncbi nlm nih gov , it is plausible that Pakistan’s CVD mortality rate has also risen during this period. However, without specific data for 2021, precise figures cannot be provided.
The risk factors that contribute to CVDs are sedentary lifestyles, smoking, and alcohol consumption. Similarly, high sugar levels, cholesterol, and fatty acids are also leading factors toward the advancement of CVDs. Other risk factors for developing CVDs are age, family history, diabetes, obesity, physical inactivity, and stress, etc. The methods to diagnose CVDs include electrocardiography (ECG), echocardiography, magnetic resonance imaging (MRI), advanced molecular imaging, and cardiac immunoassays. They proved to be one of the effective methods for CVDs diagnosis with high accuracy. Currently, CVDs cannot be cured completely, but they can be controlled in many ways. They can be prevented by taking preventing measures such as diet control and exercise. There are mostly treated by taking medicinal drugs. Sometimes, medicinal drugs are taken in form of a poly-pill, which is a combination of different drugs that help in treating CVDs. In worst cases, patients have to go through different surgeries. However, cardiac surgeries have some limitations such as physically weak patients or elderly, co-morbidity patients having other diseases such as diabetes mellitus and immunocompromised patients, are not compatible for surgeries.
The therapeutic capabilities of agents through Nano systems are improved by at least 3 different methods, including nucleic acids, small-molecule drugs and proteins, gas-signaling molecules, and stem cells. These biomedical systems deliver these distinct therapeutic agents to the targeted region. Nano systems serve as effective delivery methods because they provide both sustained release and local therapeutic benefits. For instance, injectable hydrogel, drug delivery systems that combine nanocomplexes alongside therapeutic agents result in better drug distribution to the targeted site. Nano systems provide a way to control drug delivery rate, such as nanoparticles (NPs), including liposomal amiodarone and platelet-like Fuso genic liposomes that decrease drug side effects. The tactical utilization of Nano systems produces improved therapeutic results in cardiovascular medical scenarios.
Nanotechnology is going to play a big role in treatment of CVDs in near future by using NPs and nanomaterials such as CNTs, organic NPs, inorganic NPs, metal NPs, and dendrimers, etc. ( Figure 1 ) and can provide us with better medical instruments, therapeutic, and diagnostic technologies. Studies are being done to develop nanomedicines and nano-carrier based drug delivery systems that can help in overcoming the conventional diagnostic systems. Nanomaterials can also be used for developing implants such as heart valves, defibrillators, vascular grafts, pace markers, and stents, etc. The implementation of nanotechnology delivers precise drug distribution systems to erase abnormal heart muscle tissues together with methods to control arrhythmias and minimize postoperative atrial fibrillation, abnormal heart muscle cells, management of arrhythmias, and postoperative atrial fibrillation. Medical research indicates drug-containing NPs might help treat severe and threatening conditions that could lead to death. Mesoporous silica NPs MSNPs improve the therapeutic properties of honokiol for suppressing neointimal hyperplasia.
Schematic diagram showing different type of nanomaterials, their classification, and characteristic features.
Conventional Procedures for Diagnosis and Treatment of CVDs
Cardiovascular MRI is a clinically recognized, reliable, and broad imaging modality for the wide spectrum diagnosis of CVDs. Due to its outstanding reliability, cardiovascular MRI is the best technique for the evaluation of variations in ventricular constraints. Its significant applications are in the assessment of left ventricular function in patients with poor echocardiographic inspections; RV evaluation; myocardial sustainability imaging; evaluation of congenital heart, aorta, and valvular diseases. Another procedure used for the diagnosis of CVD is ECG, which has a significant clinical effect on examining the severity of CVDs. The ECG signifies an electrical tracing of the heart and is recorded noninvasively. ECG is used to detect myocardial damage, ischemia, earlier infarction, and Rheumatic heart disease . It is also helpful for the evaluation of blunt cardiac trauma. In the diagnosis of congenital heart diseases, electrolyte imbalance, and rhythm disorders, diagnosis tool in a sports physical exam to rule out cardiomyopathy. Echocardiography is most commonly used method to assist the structural components of heart. It is used for diagnosis at cellular and subcellular level such as detection of specific tissue epitopes etc. It uses different imaging techniques and probe utilization to create variety of biomolecules.
There are many pharmaceutical drugs that are used for treatment of CVDs. Clopidogrel bisulfate irreversibly modifies the platelet and inhibits platelet aggregation. It involves adenosine diphosphate receptor and blocks its proaggregatory effects and contains different drug metabolizing enzymes. Warfarin is an antagonist that is commonly used as an anticoagulant for treating patients with atrial fibrillation. The drug inhibits epoxide reductase enzyme, which results in a decrease in vitamin K-dependent coagulation factor’s activation. Higher levels of low-density lipoprotein represent the core danger factor when it comes to CVD development. Fibrates possess 2 essential therapeutic functions, including atherogenic dyslipidemia modification and triglyceride serum reduction. Acetylsalicylic acid (Aspirin) works as an anti-inflammatory and antithrombotic medication that permanently blocks COX-1 by acetylating serine 520 in platelets, thus, reducing platelet production of prothrombotic thromboxane A2.
A poly-pill is a fixed dose combination pill used for the prevention of CVDs. It simplifies the treatment regimen, reduced the cost, and has prevented up to 88% of heart attacks and strokes. Since the poly-pill’s individual components are all very effective for secondary prevention of CVD, it is estimated that the poly-pill will also be effective. The poly-pill that combines 3 to 4 pharmaceutical components having potential to reduce major cardiovascular risk factors includes “multipurpose” or “cardiovascular” poly-pill. ACE inhibitors are used in patients having hypertension, heart failure, coronary artery disease, chronic kidney disease, and diabetes. ACE inhibitors block the angiotensin II type 1 (AT1) and angiotensin II type 2 (AT2) receptors and inhibit the formation of angiotensin II. This results in blockage of the vasoconstrictor actions of AT1 receptor. Beta blockers are also used to reduce major cardiovascular events such as stroke. Beta blockers inhibit renin angiotensin by inhibiting the release of renin from the kidney. Ivabradine is utilized in the cure of various CVDs including coronary blood vessel disorder and heart malfunction. Ivabradine is a new and only offered HCN inhibitor, which can lower the higher heart rate and also improves myocardial oxygen quantity by delaying diastole.
Cardiac surgeries
The first cardiac surgery was performed by Axel Cappelen on September 4, 1895. Since the different types of cardiac surgeries have now been performed for various types of heart issues. Balloon angioplasty is one of them, which was first invented by Grundig on Sept 16, 1977. Although it is effective in treating coronary stenosis, but the patient gone through it had high rate of abrupt vessel closure that resulted in repeat dilation or bypass surgery, and the patient had high rate of restenosis that occurred in the treated vessel segment. Because of these limitations, it is usually combined with stent implantation. These devices have been revolutionized for the treatment of coronary artery diseases because they have biodegradability and excellent biocompatibility and also reduce the incidence of restenosis. Another surgery includes heart transplantation because of refractory heart failure and total artificial heart surgery is done by replacing patient’s ventricles and valves by a pneumatically powered artificial heart because of biventricular heart failure. Although it improves the quality of life of the patients with end-stage heart failure but the scarcity of heart donors makes it difficult and it has many complications such as Primary graft failure, Right ventricle dysfunction, bleeding, thrombosis, renal failure, chronic anemia, infections, and rejection.
Coronary artery bypass grafting is the most preferred surgical procedure for restoring obstructed coronary arteries worldwide, with improving blood flow and oxygen supply. Aortic valve repair or valve replacement is a surgical method that is used to replace or repair the aortic valve that is dysfunctional. It is a recognized method that has shown excellent stability in patients with valve repair. This technique has led to the enhancement in the reproducibility and dissemination of AV repair. Implantable cardioverter-defibrillator is a small electrical device for monitoring and regulating abnormal heart rhythms by sending electrical pulses and helps to prevent sudden cardiac death. However, in some cases they can cause potential device infection and inappropriate shocks, worsening the quality of life. So they are not considered a high priority treatment and secondary prevention of sudden cardiac death. Artificial cardiac pacemakers (PMs) are tiny electrical appliances that recognize intrinsic cardiac beat and convey electric signals, if suggested, to accelerate the heart and switch the malfunctioning pure pacemaker, but they are not preferred because they can cause blood clots and infections.
Single-cell RNA sequencing in CVDs
Both clinical professionals and scientific researchers maintain cardiovascular health promotion as an ongoing essential task. The contemporary method for studying RNA transcripts inside single cells uses Single-cell RNA sequencing technology which scientists call scan-seq. The methodology delivers knowledge about cell composition together with cell-specific functions within highly structured tissue structures and body systems of organisms. Scientific research that embraces scorns-seq techniques has generated extensive information across various fields leading to valuable discoveries about human and model organism and plant cell structures. The research developments based on this investigation led to the growth of cell numbers which created a new pathway for high-throughput RNA sequencing execution. The development of modern single-cell RNA sequencing tools, including enhanced methods for sample collection as well as barcoded reverse transcription, cellular isolation, cDNA enhancement, library construction, sequencing, and bioinformatics has been made possible. The new technological developments achieve both cost-reduction, automated workflow advancement, and increased processing speed. The basic principle of scRNA-seq has endured unchanged while additional solutions have been established. This technological advancement will boost the clinical and personalized healthcare applications of this approach. Single-cell RNA-seq technologies have become extensively used for studying heart diseases as part of modern CVD research.
Cardiovascular biomarkers
The field of cardiovascular diagnosis depends heavily on biomarkers, especially cardiac troponins (cTnI and cTnT) alongside natriuretic peptides (BNP and NT-ProBNP). The regulatory proteins known as cardiac troponins prove vital for muscle contraction when myocardial injuries occur, particularly during MI. The detection of myocardial damage results in bloodstream liberation of these proteins as specialized detectors for diagnosing cardiac muscle injuries. Medical professionals heavily affirm the importance of this specific characteristic because it enables the detection of cardiac events while excluding other types of muscle tissue damage. The clinical significance of cardiac troponins exists in their ability to both identify heart attacks and analyze how troponins escape from cardiac cells and decay in the blood. The analytical data give doctors essential knowledge to determine when and how much myocardial damage occurred. Doctors recognize elevated levels of cTnI and cTnT as the definitive methods to diagnose MIs.
The 2 natriuretic peptides BNP and NT-ProBNP used together with cardiac troponins enable healthcare professionals to obtain important diagnostic and management information about HF. Blood cells produce these peptides as a reaction to increased ventricular stress and volume problems that characterize HF. The peptides participate actively in preserving cardiovascular stability by supporting nitrituria and diuretic effects while dilating blood vessels. The diagnostic value of HF is provided by BNP and NT-ProBNP tests, which display elevated levels in conditions that increase intracardiac pressure and lead to ventricular dysfunction. NT-ProBNP stands out for its prolonged blood circulation duration and stable characteristics in bloodstream, which makes it an ideal biomarker for chronic heart failure examinations. The study by Bianucci investigates the latest biomarkers for HF diagnosis beyond commonly used BNP. Their research showcases the combination between advanced optical sensors and their methods with advanced optical sensing technology through high-performance liquid chromatography and LASER/LED-induced fluorescence and Raman spectroscopy. Nanotechnology and microfluidic technologies boost the functionality of optical methods to detect patterns of multiple markers in whole blood and serum clinical specimens.
Use of Nanotechnology for the Diagnosis and Treatment of CVDs
Molecular imaging of CVDs based on nanotechnology
NPs are perfect for imaging due to their flexibility, elevated surface to volume proportion, and excellent bioavailability increased the accuracy of clinical imaging purposes. AuNPs have effectively utilized in the cardiovascular field because of their necessary bioactivity and mobility.
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Photoacoustic imaging in which AuNPs can be involved depend on the temperature variations of nano agents when vibrated laser rays are absorbed.
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Optical coherence tomography (OCT) is an additional technique for CVD imaging utilizing AuNPs. In OCT, the infrared wave is directed to the target nerve from coherent beam supply and an image is constructed dependent on the back-dispersed beam. It demonstrated that specific cells held in biocompatible solutions can be recognized utilizing cardiovascular OCT.
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MRI is a non-invasive methodology that could deliver broad vasculature information that is crucial for the useful CVD analysis. Gd is frequently applied in MRI to generate a positive indicator because of its superior paramagnetic ability as a T1-based contrast media. Super magnetic iron oxide nanoparticles (SPIONs) are also frequently utilized as MRI contrast media. For enhanced accuracy and bioavailability, the Fe3O4/Gd2O3 NPs have been covered with harmless 3,4-dihydroxyhydrocinnamic acid (DHCA).
Superparamagnetic NPs
The sensitivity of MRI could be enhanced with contrast media like iron oxide nanoparticles (IONPs). IONPs have been broadly researched and used as imaging agents for analysis of cardiovascular (CVD) disorders. IONPs are also known as super magnetic IONPs (SPIONs) because they perform outstanding magnetic functions. The single effective IONPs presently being utilized as an MRI contrast media for the CVD structure is ferumoxtran. SPIONs can change the basic contrast possessions of organic tissues precisely by altering the proton concentration of a tissue, and secondarily by changing the easing properties of nearby H protons, altering the local magnetic field and thus its relaxation period T2 amounts. All of the IONPs created to aim at the monocyte-macrophage, both passively and by actively aiming macrophages with dextran, d -mannose, and antibodies. IONPs could also be incorporated with ligands to aim for platelets, vascular smooth muscle cells, monocytes, fibrin, and macrophages. IONPs can be coupled with ligands to support position-specific communications and improve their supply to the target of our interest. The targeted IONPs effectively gather at the target site and could increase MR images by stimulating contrast agent ( Table 1 ).
Table 1
Medications among patients with coronary heart disease
| Medications | Proportion with treatment (%) |
|---|---|
| Aspirin | 97 |
| Beta-blockers | 81 |
| ACE inhibitors | 38 |
| Angiotensin II blockers | 16 |
| Statins | 91 |
| Clopidogrel | 31 |
| Diuretics | 38 |
| Calcium channel blockers | 78 |
Targeted drug delivery system
A variety of delivery systems exists for treating CVDs. Drug carriers showing nontoxic attributes together with immune system evasion capacity and biodegradability with compatibility to biological conditions, and immune system nontriggering ability and targeted drug delivery functions are considered the ideal properties. Different parameters, such as pH, temperature, enzyme activity, and stimuli, and more, enable the achievement of targeted drug delivery systems. NPs of polymeric and liposomal structures have diagnostic and therapeutic abilities by incorporating multiple drugs into their structures, while other NPs need to combine functional ligands before drug binding. The drug targeting process, along with stability enhancement and improved surface ratio, requires surface modification of NPs through functional agents, including peptides, aptamers, antibodies, and so on.
Magnetic NPs
These particles are created to target particular receptors in tissues and are close to go through clinical trials for CVD purposes. Their biocompatibility, superparamagnetic, nonorange mass, and surface covering properties allow selective attachment for site-specific delivery. SPIONs are appropriate for in vivo observing of the stem cells due to their exceptional magnetic properties. Modified SPIONs were injected into random sections of the pre-enacted region to transport the cells into the damaged portion of the myocardium, devoid of open-chest surgical treatment. An FDA-approved SPION, ferumoxytol (which is an intravenous (IV) iron product substitute utilized to treat anemia), is doubly conjugated with anti-CD45 and with antibodies located in damaged cardiomyocytes. The double antibody-conjugated NPs aided elevated affinity attachment of cells to damaged cardiomyocytes equally in vitro and in vivo. The attained outcomes report that this method can cure severe MI.
Gold NPs
Gold NPs are usually inert materials that are made up of gold particles of the size of 1 to 100 nm. They have their applications in drug delivery and molecular labeling because of their properties such as easy to synthesize, high surface plasmon resonance, high absorption capability, low immunogenicity, low cytotoxicity, stability, biocompatibility, and their ability to bind with targeted materials. They decompose in a proper environment once they reach the targeted sites and are renally excreted through the body. They have efficient antioxidant properties that help them to deal with CVD. The photo thermal property of gold NPs helps in the diagnosis of photo thermal revascularization of blocked arteries ( Table 2 ).
Table 2
The report mentions cardiac biomarkers together with their role in diagnosing heart failure pathophysiology
| Influence on heart failure | Biomarker types | |
|---|---|---|
| 1 | Myocardial injury | Troponin, H-FABP |
| 2 | Inflammation | IL-6, TNF-α, IL-1-Beta, CRP |
| 3 | Remodeling | sST-2, Galectin |
| 4 | Fibrosis | TGF-ß |
| 5 | Mechanical stretch | BNP, GDF-15 |
| 6 | Neurohumoral | Copeptin, Endothelin-1 |
| 7 | Oxidative stress | Uric acid, Myeloperoxidase |
| 8 | Micro RNA | miR-18a-5p, miR-26b-5p, miR-27a-3p, miR-30e-5p, miR-106a-5p, miR-199a-3p, miR-652-3p, miR-30c, miR-221, miR-328, miR-375, miR-423, miR-34a, miR-21-3p, miR-199, miR-30a |
The drug delivery effectiveness of clinical drugs leaps forward when gold NPs come into play for conjugation purposes because Simdax shows enhanced coronary disease treatment along with metoprolol becoming more effective for cardiac tissue delivery after coupling with gold NPs. The diabetic cardiomyopathy therapeutic treatment involves miR155-AuNPs or gold NP antagonist. Different target sites exist for gold particles that possess diverse dimensions. Gold NPs measuring below 200 nm penetrate and accumulate within the ischemic muscle tissue using their enhanced permeability and retention effect that enables medication delivery to exogenous growth factors for recovering substantial volumes of ischemic tissue. The size reduction of infarcted hearts occurred through PEGylated gold NPs (10 nm size) that prevented necrosis and apoptosis in cardiomyocytes because PEG coating increases hydrophilicity and stability in circulation time. Studies demonstrate that gold NPs find medical applications in CVD, including photo acoustic imaging that functions as optical or ultrasound imaging as well as electrochemical detection and diagnosis alongside photothermal therapy.
Polymeric NPs
The fundamental goal of cardiovascular disease treatment focuses on the ability of polymeric NPs to show adjustable characteristics together with body absorption capacity. Polymeric NPs serve 2 functions by staying either attached or free as new substances. Polymeric nanomaterials incorporating polyester with carbon nanotubes (CNTs) improved their electric conduction properties causing increased strength for enhanced cell–cell connection applications in CVD treatment. The nanodrug distribution system uses polymeric Poly (lactic-coglycolic acid) (PLGA) NPs to influence monocyte-derived irritation in atherosclerosis ( Figure 2 ). The effectiveness of polymeric PLGA NPs as a drug delivery system is supported by the fact that they enfold pioglitazone while also significantly decreasing the amount of fibrous caps and enlarging fibrous caps.
Nanodrug delivery systems facilitated a cure for severe coronary disorder. The figure shows a nanodrug delivery system facilitated cure for patients with unreliable plaque through (A) intravenous injection (IV) plus (B) distribution to mingling monocytes, with (C) healing aim consisting atherosclerotic plaque balance and inhibition of severe myocardial infarction.
PEG-based NPs
Polyethylene glycol (PEG) is a biocompatible material often coated on the surface of NPs, which enhances the circulatory lifetime of the drug delivery system. A smooth conductive hydrogel was manufactured comprising of a multiple armed PEGDA700-Melamine (PEG-MEL) crosslinker for cardiac repair. The PEG-MEL could cross-linkage with thiol-altered hyaluronic acid to make an injectable hydrogel quickly. To enhance the therapeutic capability of the hydrogel, adipose tissue-developed stromal cells were included ( Figure 3 ). After an infusion in the MI region in a rat, general improvement of heart function was noted.
Diagram showing the function of PEG-MEL/HASH/GO based nanoparticle hydrogel system including ADSCs for heart restoration by shot into the myocardial infarction region of rats, with the aim of improving the spread of automated and electric indicators to restore cardiac function.
Nanocarriers (liposomes, micelles dendrimer, and CNTs)
The vesicle structure of liposomes contains bilayer phospholipids with dimensions ranging from 50 to 200 nm. Research shows the vesicles can exist in different structural forms due to varying lipid molecule dimensions and chemical makeup and elasticity. Liposomes contain analogies of structure that have both hydrophobic and hydrophilic characteristics which enable them to serve as effective delivery systems. Scientific research has demonstrated that drug compounds embedded inside liposomes create a therapeutic approach which results in lower toxicity than typical free drug treatments for cardiovascular disorders. Surface modifications of liposomes can be achieved through PEG coating or targeted delivery through antibody or other targeting chains attachments for improved biological system residence. Liposomes have many therapeutic applications, function as therapeutic agents for peripheral artery disease patients and patients dealing with intermitted claudication. The systems show significant value but their short-term stability issues result in premature drug discharge. The technique requires using larger ratios of excipients to drug components leading to increased production costs which makes it less effective compared to polymer-based systems per study.
The amphiphilic polymeric micelle structure forms aggregate solutions when their dimensions measure <100 nm in size. The drug encapsulation area inside micelles remains hydrophobic while the outer shell provides hydrophilic properties to increase circulation duration. The administration of therapeutic water-soluble compounds through micelles stands as the most promising treatment method for CVDs drug delivery systems according to Zheng et al. The dynamic structure of polymeric micelles represents an advanced drug delivery system because it supports multiple drug loading possibilities, targeted ligand attachment, and reduces dissolution rates. An excellent drug delivery system, which exhibited sensitivity to the oxidative atherosclerotic plaque microenvironment, was presented in 2018. Block copolymer micelles composed of poly-ethylene glycol and poly-propylene sulfide (PEG-PPS) served to solubilize andrographolide while decreasing both inflammatory response and reactive oxygen species levels for atherosclerosis therapy.
The dendrimer molecular structure features a compartmentalized branching structure that exhibits exceptional solubility characteristics, along with high precision distribution, minimal antigenic traits, and enhanced durability properties. The size ranges of dendrimers are from 1 to 5 nm. A spherical form of synthetic dendrimers results from polymerization operations to create internal voids inside the molecular structure. Their drug delivery function receives support from exceptional drug encapsulation capabilities. When used as a platform for conjugation with biocompatible compounds, dendrimers enable the achievement of high permeability together with reduced toxicity. Doctors can implement various modification strategies to achieve higher therapeutic delivery accuracy of drugs. Polyamideamines represent the primary dendritic molecules, which contain nitric oxide as a free radical variety. The drug delivery capability of vascular smooth muscle makes this compound useful for various CVDs applications. The storage of cardiac functions was enhanced by using siRNA-based oligo-arginine-conjugated dendritic delivery systems to silence ATIR expression in cardiomyocytes through improved siRNA internalization in these cells. Dendrimers serve as adaptable nanocarriers which assist in antithrombotic protection and cardio-protection through delivery of drug-resistant hormone mimetic compounds. The high number of surface branches on dendrimers generates toxicity risks due to their exceptionally cationic or anionic nature according to Kashyap et al.
The high aspect ratio of CNTs is accountable for their effective drug loading capability and regulated drug delivery to the target area. CNTs are effective to stimulate neonatal rat ventricular cardiomyocyte spread, development, and enhanced electrical performance. Multiwalled carbon nanotubes created close connections with neonatal rat ventricular cardiomyocyte cell membranes are found by conducting transmission electron microscopy ( Figure 4 ). This discovered the ability of CNTs as biocompatible probes for use in cardiomyocyte studies. Highly refined single-walled CNTs had no lethal consequences on the H9c2(2-1) rat cell line as noticed by an assessment of cell increase and sustainability versus programmed cell death and of structural variations under light microscopy, encouraging additional work for CVD diagnosis and therapy ( Table 3 ).
Association of CNT with cardiac myocyte membranes ( arrows ). The figures exhibit a close interaction between the CNT and cardiomyocyte cell membrane.
Table 3
Nanocarriers studied for the efficient treatment of cardiovascular diseases
| Types of nanocarriers | Drugs used in the treatment of CVDs | Biological functions | Limitations of the drugs | Advantages of nanoplatforms | References |
|---|---|---|---|---|---|
| Liposomes | |||||
| Liposomal nanoparticles coated with PEG | Prednisolone phosphate | Best for atherosclerotic disease | Short half-life in circulation | Increase the drug’s half-life to 45–63 hour in humans | |
| PEGylated liposomes, with a peptide sequence of fibrinogen gamma chain | Recombinant tissue plasminogen activator (rtPA, (alteplase)) | Plasminogen activators | Short half-life of rtPA | Improved thrombolytic activity | |
| Metallic nanoparticles | |||||
| Gold | Vascular endothelial growth factor (VEGF) | Severe hindlimb ischemia is treated | Short half-life of VEGF in circulation | Targeting rate is high | |
| Gold | Mesenchymal stem cells (BMSCs) derived from bone marrow | Potentiates the cardiogenic differentiation of stem cells | Control ability to differentiate into multiple lineages | Enhanced cellular and functional effects on the regrowth of infarcted myocardium | |
| Gold | Levosimendan (Simdax) | Inotropic agent contraction of myocardial is increased in heart failure related patients. | Preferential targeting Simdax to the target heart tissue decreased | Having vital cardio protective effects in rats with doxorubicin-induced heart failure | |
| Silica nanoparticles | |||||
| PEGylated mesoporous-silica | Pueraria | Best for the treatment of cardiovascular diseases |
Short half-life in human
High doses of puerarin. |
Improved blood compatibility with low hemolysis | |
| Polymeric nanoparticles | |||||
| Dendrimer | Hirudinea | Antithrombotic and anticoagulant agent | Short plasma half-life, generates permanent hirudin-thrombin complex | Transfer gene to thrombosis and its treatment | |
| Micellar | Hirudinea | Natural thrombin inhibitor | Short plasma half-life | Stop the formation of fibrin clots after coronary artery occlusion | |
| Polymeric micelles | m-Tetra (hydroxyphenyl) chlorin (mTHPC) | Anti-inflammatory agent | Side effects and other off-target effects | Increased stability and thus allow accumulation of intact mTHPC- to macrophages of atherosclerotic lesions | |
Self-emulsifying drug delivery system
The development of lipid-based drug delivery systems tries to enhance absorption rates of lipophilic pharmaceuticals. The pharmaceutical formulation known as self-emulsifying drug delivery systems (SEEDS) represents one type among these formulations. SEEDS consist of natural as well as synthetic oils and solid/liquid surfactants or hydrophilic solvents that mix into isotropic solutions. The absorption and availability increase for drugs due to SEEDS while they defend the drug against harmful conditions in the gut environment. The system produces nano-emulsion droplets inside the gut while following the lymphatic route to reach the target. SEEDS maintain prolonged stability throughout time while offering convenient handling properties.
Nano emulsions
Formulation of nano emulsions to enhance therapeutic effectiveness and protection of antihypertensive medications, many other formulations can be created utilizing nanotechnology. For instance, the formulation of curcumin in a nano emulsion structure with the objective of lowering its undesirable solubility and bioavailability. The curcumin nano emulsion demonstrated improved ACE retardation contrasted with natural curcumin. This discovery proves that the curcumin nano emulsion structure has enhanced bioavailability and solubility. Preparation of protein-filled perfluorocarbons (PFCs) nano emulsions is used to deliver therapeutic proteins to heart for the therapy of cardiac disorders. Perfluorocarbons (PFCs) are inert substances with great biocompatibility and solubility. In vivo findings demonstrated that the protein filled perfluorocarbons nano emulsions effectively supplied proteins to the myocardial muscle of mice and decreased ischemic myocardial damage produced by severe MI.
NP drug eluting stents
The present stent technologies have some limitations such as formation of in-stent restenosis, which can be improved by using nanotechnology. It can be used for prevention of smooth muscle cell proliferation by antirestenosis strategy and restoring functional endothelium by prohealing strategy. Antirestenosis strategy prevents in-stent neointima formation by NPs assisted delivery of antiproliferative and anti-inflammatory agents or by heat induced death of inflammatory cells using light/radiation activated NPs. The prohealing strategy involves reendothelialization, by using nanofibrous scaffold which acts as extracellular matrix, enhancing the cells proliferation under the stent in presence of magnetic field by using magnetic NPs. In order to achieve these strategies, stents are coated by biodegradable polymeric blends and NPs to form drug eluting stents, which can act as drug carriers.
Hydrogels
Hydrogels are hydrophilic polymeric networks capable of absorbing large volumes of biological fluids that facilitate controlled drug-release. Because of their high biocompatibility they are used as attractive drug delivery vehicles. They can bind with various moieties such as NPs, slabs, microparticles, coatings, and films. External stimuli such as hydrolytic, enzymatic, or environmental stimuli are sufficient to control the hydrogels to release drug at the desirable site. The major issue in this includes toxicity which occurs after the degradation of hydrogels by residual monomer, cross-linker, and catalysts. There are distinct material-based hydrogels used in percutaneous coronary intervention. These strategies help in the recovery of damaged cardiac tissues while in some severe cases implantation of ventricular assist devices is required. Although hydrogels have shown their ability to be used in percutaneous coronary intervention but it still lack the required mechanical strength, enzymatic activity, and bioactivity.
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