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Chapter 15
Drug Delivery to the Cardiovascular System: Application
and Future Prospects
Pankaj Kumar Umar, Jyoti, Asha, and Sachin Kumar Jain
Abstract
Cardiovascular disease (CVD) constitutes one of the world’s prominent health threats, generally leading to
unfavorable enduring outcomes. The new molecular and genetic knowledge of CVD is ever-expanding;
consequently, this has brought about the innovation of cell and molecular therapies that carry hope for
treatment. Advanced approaches have been employed to enhance the effectiveness and the period of these
therapies, some of which involve new agents alongside biological ones. Targeted dr ug delivery to the
cardiovascular system, in particular, is seen to hold much promise with several main advantages. This
approach enables a more precise and ef fective delivery of therapeutic drugs directly to the heart and
blood vessels, enhancing treatment outcomes while minimizing undesirable side effects. However, at the
same time, there remains several impediments that have to be addressed to realize the formulation of
effective systems for the delivery of drugs to the cardiovascular system. Work actively ongoing in Cardiovascular Drug Delivery Specialty Section aims to do these in order to help these new approaches enter the
clinics. These efforts aim to ultimately reduce the global burden of cardiovascular diseases. Also, there is a
need to conduct additional research for the improvement of the design and str ucture of drug delivery
systems as well as the external factors applied in the control of drug delivery within the body so that the
therapies would be maximally efficient and safe with few undesirable effects.
Key words Targeted drug delivery, Novel therapeutic methods, Cardiovascular disease, Cardiovascular drug delivery specialty section, Decreasing the unwanted effects
1 Introduction
The diseases of the cardiovascular system, such as ischemic heart
disease and stroke, have become a worldwide public health problem
with rapid morbidity and mortality rates up to now more than any
other diseases [
role in maintaining overall health. The disruption of the system can
result in the development of CVD such as atherosclerosis, myocardial infarction, and small blood vessel disease. A major risk factor
for CVD is high blood pressure, also known as essential hypertension. When considering the severity of symptoms Developing
1]. The cardiovascular system plays an important
335
336 Pankaj Kumar Umar et al.
effective treatments for CVD has therefore become a top priority.
Rapid advances in nanoscience and the unique properties of nanomaterials have brought nanotechnology as a promising solution to
the challenge of treating cardiovascular diseases. Nano-drug delivery systems (NDDS), a type of nanomaterial, offer several advantages in drug delivery. These systems can increase drug stability and
water solubility, extend circulation time, improve absorption by
ta
rget cells or tissues, and reduce the degradation of enzymes
This increases the
2, 3].
[
Nano-drug delivery systems (NDDS) can be administered
through multiple routes, such as inhalation, oral administration,
or intravenous injection, and improving drug absorption. In the
past few years, researchers are increasingly interested in developing
nanomedicine carrier systems for the diagnosis and treatment of
heart diseases, and concerns about the potential risks of exposure
associated with these materials are also increasing. When you touch
more, nanomaterials are also more likely to interact with blood
vessels, blood, and their components. This may have a significant
impact on human health [
Giving m
important foundation of modern medicine for a long time. According to the theory, various diseases arise due to the presence of
abnormal or diseased cells within otherwise healthy organs and
tissues. Drugs must hit a specific target molecule in order to be
effective. However, all drugs are inherently toxic to some degree.
This may restrict the safe dosage and consequently reduce the
drug’s treatment efficacy in order to minimize the risk of side
effects. It is important to target drugs directly to diseased organs
and cells. To achieve this goal, drug delivery systems (DDS) play an
important role in enhancing the safety and efficacy of therapeutic
agents. Recent integration has led to the development of
nanoparticle-based drug delivery systems (nano-DDS). These systems can modify the behavior of medical and diagnostic substances
within the body. One of its main objectives is to modify the kinetics
in the body to improve effectiveness [
Nano-drug
using materials and structures. Nano-drug delivery systems
(nano-DDS) can be designed using various materials and structures, including lipids for forming micelles or liposomes, polymers,
dendrimers, carbon nanotubes, iron oxide crystals, gold nanoparticles, and other metallic nanoparticles [
highlight specific examples of nanoscale materials that have been
evaluated as nanodrug delivery systems (nano-DDS), for example,
micelles formed from synthetic amphiphilic molecules, such as
lipids and polysaccharides [
aqueous environments and can encapsulate hydrophobic therapeutic agents, helping to address solubility challenges. Their size
safety and efficacy of dr ugs used to treat CVD
4].
edicines a
nd other medical substances, it has been an
.
5]
delivery systems (nano-DDS) can be fabricated
6]. In this section, we
Micelles naturally self-assemble in
7].
Drug Delivery to the Cardiovascular System: Application and Future Prospects 337
typically ranges from 10 to 100 nanometers in diameter, with more
confined internal spaces compared to liposomes. Liposomes, primarily composed of phospholipids that form bilayer structures with
an internal aqueous compartment, vary in size, often spanning from
a few hundred to several thousand nanometers in diameter. Among
nano-drug delivery systems (nano-DDS), liposomes have been the
most extensively studied in both basic and clinical research, with
approval f
(FDA). They
chemicals, nucleotides, and crystalline metals [
rom the United States Food and Drug Administration
can incorporate a variety of substances, including
8].
At present, two polymers, polylactide (PLA) and poly(lactideco-glycolide) (PLGA), are utilized in the synthesis of
FDA-approved biodegradable polymeric nano-drug delivery systems (nano-DDS). PLGA polymers are capable of encapsulating
both hydrophilic and hydrophobic therapeutic agents, such as chemicals and nucleotides, through emulsion solvent diffusion techniques. These systems are being investigated for the treatment of
challenging diseases, including cardiovascular conditions [
9]. Den-
drimers are highly branched macromolecules featuring a precisely
controlled, nearly monodisperse, three-dimensional structure that
radiates from a central core. Polymer growth begins at this central
core and expands outward through successive polymerization reactions, which determine the overall size of the dendrimers, typically
starting at a few nanometers. The core’s cavities, along with the
folding of the branches, form cages and channels that can encapsu-
10]
arbon nanotubes, a type of fullerene,
late therapeutic agents [
. C
are composed of graphite sheets rolled into tubular structures. The
diameter of single-walled nanotubes typically ranges from
0.5 to 3.0 nanometers, while their length can vary from
20 to 1000 nanometers. Therapeutic agents can be attached to
either the inner or outer surfaces of the nanotube walls, referred
to as filling or wrapping modes of binding, respectively [
In contrast,
ity. Iron oxides are typically synthesized through an alkaline
co-precipitation process involving Fe
metallic nanopar ticles possess inherent functional-
2+
and Fe
3+
salts in an aqueous
11].
solution, along with a suitable hydrophilic polymer such as dextran
or poly(ethylene glycol). This method produces an iron core with a
diameter of approximately 4–5 nanometers, characterized by a
hexagonal shape. Surrounding this iron core, dextran or poly(ethylene glycol) molecules form a protective layer, resulting in the
creation of superparamagnetic iron oxide particles (SPIO), which
range from 60 to 150 nanometers in size. These SPIO particles
serve as effective contrast agents for magnetic resonance imaging
(MRI), enhancing the visibility of tissues and structures within the
body during imaging procedures [
12].
Gold nanoparticles exhibit
unique photodynamic properties, allowing them to absorb nearinfrared light and subsequently emit both light and heat. These
characteristics have been explored for use in cancer photothermal
338 Pankaj Kumar Umar et al.
therapy. Additionally, gold nanoparticles can be conjugated with a
variety of therapeutic agents and targeting ligands, functioning
effectively as drug carriers. The intravital kinetics of nano-drug
delivery systems (nano-DDS) can vary significantly; their behavior
in biological environments is influenced not only by their size but
also by their chemical composition and morphology. However, size
remains the most critical factor determining the physiological
be
havior of nano-DDS [
Cardiovascular disease (CVD) continues to pose a significant
global health challenge, often resulting in unfavorable clinical outcomes. With advancements in our understanding of the underlying
genes and molecular mechanisms, cell and molecular therapies have
emerged as promising new treatment strategies for CVD. Nevertheless, early studies have shown disappointing outcomes due to
insufficient delivery to the intended sites and inadequate expression
of genes or successful engraftment of cells [
micro/nano particles (MNPs) have enabled the development of
sophisticated drug delivery systems (DDSs) that are capable of
targeted delivery and controlled release [
acteristics of new materials that respond to changes in their surrounding environment have motivated researchers to create more
intelligent drug delivery systems (DDSs) capable of reacting to
specific and predictable stimuli at the target site. Currently, stimuli
such as magnetic fields (MF) and ultrasound (US) can be employed
to initiate the release of drugs [
design of smart drug delivery systems (DDSs) may enable these
vehicles to respond to multiple combinations of various stimuli,
enhancing site specificity and improving controlled delivery [
13].
14]. Advancements in
15]. The fascinating char-
16]. Moreover, the sophisticated
17].
2 Delivery of Small Molecules
Traditionally, small molecules have been the primary form of treatment for cardiovascular diseases. Widely used dr ugs in this category
include atorvastatin, metoprolol, valsartan, and ezetimibe, which
are typically available as oral medications and are used for long-term
management of cardiovascular conditions. Given the immense market value in cardiovascular treatment, which amounts to billions of
dollars, there is substantial interest in developing new medications
as well as improving delivery systems for these existing drugs.
The field
cant focus of research, and several innovative technologies have
emerged over the last few decades. One of the primary challenges
in drug development is the failure of drug candidates in clinical
trials, which often occurs due to poor pharmacokinetic properties.
This issue has prompted a shift in the drug discovery process,
leading to the earlier integration of pharmacokinetic factors such
as absorption, distribution, metabolism, elimination, and
of small molecule drug delivery has become a signifi-