INTRODUCTION
Recent
years have seen a significant increase in theoretical and experimental studies
on the subject of blood flow in arteries with stenosis from a variety of angles
in the field of vascular biomechanics, depending on the objectivity of the
issues in the life sciences. The plasma that makes up about 55% of the total
blood volume and is primarily made up of water, dissipated proteins, mineral
ions, clotting factors, hormones, and blood cells is what makes up human blood,
which is a heterogeneous multiphase suspension of blood cells (red blood, white
blood, and platelets) . Although total blood has a non-Newtonian fluid
character, it has been shown that plasma behaves like a Newtonian fluid . Blood
has a Newtonian character for shear rates more than 100 s-1, and this may be
seen in big arteries, veins, and cavities, among other places. Blood behaviour,
or hemo-rheological behaviour, is nonNewtonian for shear rates less than 100
s-1. One of the key parts of the circulatory system are the blood vessels.
Veins are responsible for delivering deoxygenated blood towards the heart,
while arteries transport oxygenated blood from the heart to various regions of
the body. Capillaries, veins, and arteries make up the majority of the body's
vessels. Capillaries typically measure 5 to 10 mm in diameter, but the diameter
of veins ranges from 1 to 1.5 cm. Elastic arterial diameter is always more than
1 cm and for muscular arteries, it is about 0.1-10 mm. The thermophysical
characteristics of blood are influenced by several factors, including
temperature, age, and hematocrit. According to a theory put out by Whitmore in
1968, the blood arteries divide often, and their diameter changes with
distance. According to Manton, the primary basis of a sizable class of issues
with comprehending blood flows is the idea of flow in a changing cross-section.
Although the precise cause of stenosis formation is unknown, its impact on flow
characteristics has been studied both theoretically and empirically by numerous
researchers. In order to understand how blood flow parameters, such as blood
velocity, pressure, and shear stress, contribute to the development of stenosis
and the efficacy of therapies, several studies have examined these factors
Table 1: Characteristics of Blood Cell
|
Blood Component
|
Per Microliter
|
Size (µm)
|
Percentage
|
|
Red blood cell
|
4.1-5.1 x 106
|
7-8
|
97
|
|
White blood cell
Neutrophils (4-10 x 103)
Lymphocytes Eosinophils
Monocytes
Basophils
|
62%
of WBC
30%
of WBC
2.3%
of WBC
5.3%
of WBC
0.4%
of WBC
|
10-12
6-14
-
15-20
-
|
|
Table 2: Characteristics of Plasma
|
Plasma Component
|
Component
|
Molecular Weight
|
Density (g/dl)
|
|
Plasma
Water 91%
Protein 7%
|
Albumin
Fibrinogen Immunoglobulins
Prothrombin
|
69000
340000
140000
68700
|
4.5
0.3
2.5
0.015
|
|
Other
Salt includes vitamin, lipid,
sugar etc.
|
|
|
|
II.
cardiovascular diseases
The
development and progression of cardiovascular illnesses are fundamentally
influenced by hemodynamic. Cardiovascular illnesses are brought on by the build-up
of macrophage white blood cells, low-density lipoproteins (LDL), and
cholesterol deposits on the arterial walls of blood vessels. This process
causes the arteries to harden and reduce the cross-sectional area of the blood
channel. Circulatory system disorders are common. These include several
cardiovascular illnesses that impact the cardiovascular system, such as
atherosclerosis, aneurysms, strokes, angina, etc., as well as lymphatic
diseases that affect the lymphatic system. Many of these illnesses are referred
to as "lifestyle diseases" because they progress gradually and are
influenced by a person's eating patterns, exercise routines, smoking status,
and other lifestyle decisions.
The
capacity to correctly focus medications into a particular sick zone determines
the best outcome for a wide range of cardiovascular disorders. Modern
pharmacological formulations prevent the medication from accurately localising end mass at locations of interest
despite extensive study and advancements in drug delivery. In many situations,
the medication molecules disperse and spread at random throughout the body,
leading to unfavourable side effects and a decrease in the active response to
recommended dosages. Nano-fluid dynamics is a new subfield of fluid dynamics
that focuses on fluids utilised in engineering at the nanoscale. Nanofluids
have significantly improved a variety of applications in energy systems,
business operations, transportation, the environment, and medicinal sciences.
III.
Clinical significance
The
World Health Organization (WHO) report 2019 states that CVDs are the leading
cause of mortality worldwide, with more people dying each year than from any
other cause combined. In 2016, 17.9 million deaths worldwide were attributed to
CVDs or 31% of all fatalities. Heart attacks and strokes are to blame for 85%
of these fatalities. The majority of CVD fatalities occur in low- and
middle-income nations. In 2015, non-communicable illnesses caused 17 million
premature deaths (before the age of 70), 82% of which occurred in low- and
middle-income countries and 37% of which were attributable to CVDs. The
majority of cardiovascular illnesses may be avoided by employing population-wide
measures to target behavioural risk factors such as cigarette use, poor eating
and obesity, inactivity, and problematic alcohol consumption. 28.1% of all
fatalities in India in 2016 were caused by cardiovascular disorders. The
leading risk factors for CVDs are high systolic blood pressure, air pollution,
high cholesterol, dietary dangers, cigarette use, and a high body mass index.
IV.
Nanofluids and application
Conventional
fluids (air, water, oils, etc.) offer great lubricating properties in
industrial applications, but their poor temperature characteristics severely
limit their usage. These days, a lot of research is being done on ways to speed
up the heat transfer rates of common fluids. Experimental research has shown
that adding tiny solid particles to the base fluid can significantly improve
its thermo-physical characteristics.
The
term "nanofluid," which Choi introduced in 1995, is a colloidal
dispersion of particles between 1 and 100 nm in size in a base fluid. These
nanoparticles can be liquid droplets, metallic, non-metallic, carbonic, oxide,
carbide, metallic, non-metallic, and more. Water, mineral oil, ethylene glycol,
or refrigerants all can be found in the base fluid. The Buongiorno model, a
two-component nanoscale formulation emphasising Brownian motion and
thermophoretic body force effects (originating in nuclear engineering at MIT),
and the Tiwari-Das model, a volume-fraction based doping model, are the main
foundations for both theoretical and experimental studies. Doping, or adding
nanoparticles to base fluids, has been demonstrated to significantly boost
thermal conductivity, which mainly accounts for the enhanced thermal
performance of nanofluids. Because of how they interact with biological
materials specifically, the nanoparticles used in biomedicine are also
synthetic. Due to the nanofluid's better thermal conductivity over the
traditional fluid, the rate of heat exchange in thermal systems is often
increased by employing it. As a result, a thermal system's size may be
optimised by transmitting a certain amount of heat, which makes the system
smaller, by employing nanofluids to speed up heat transfer. In comparison to
micro fluids, nanofluids are more stable and have a greater capacity to improve
heat conduction. Nanofluids are replacing traditional fluids in many
applications including heating and cooling.
V.
Drug delivery system
A
formulation or a device is referred to be a drug delivery system (DDS) if it
makes it possible to introduce a therapeutic material into the body and
increases its efficacy and safety by managing the rate, timing, and location of
drug release. Drug delivery methods alter the drug's release profile,
absorption, distribution, and elimination to increase product effectiveness and
safety as well as patient convenience and adherence. Despite extensive research
and development into medication delivery, the medicines are still unable to
localise en mass to locations of interest due to current formulations. These
medicine molecules scatter and disperse at random inside the body, causing
unfavourable side effects that lessen the effectiveness of the right amounts.
Nanofluid dynamics, a novel subfield of fluid dynamics that has applications in
biology, medicine, and energetics, has emerged in recent years. In modern
medicine, for instance, nano drugs are combined in microchannels for controlled
distribution with bio-MEMS, which is a fundamentally different application of
nanofluids (micro-electro-mechanical system). For this reason, medication
delivery using nanoparticles holds enormous potential for therapies with few
adverse effects and optimising precisely targeted distribution. Although the
platform may increase a drug's tendency to accumulate at a specified site, it
also encounters a complicated array of biological obstacles that restrict
site-specific bioavailability, impeding the realisation of adequate therapeutic
results.
The
use of nanoparticles in therapy, diagnostics, coating medical devices, and
medication administration is widespread. The magnetic targeted medication
delivery system is one of the most alluring and effective methods for
administering pharmaceuticals to the damaged spot. Due to their ability to
reduce toxicity and other negative side effects, MTDDS are becoming more and
more common in biomedicine. They are also fast-acting and extremely effective
when compared to conventional approaches. Magnetic nanoparticle (MNP) uses in
biomedicine might be either in vivo or in vitro, depending on the application.
Applications for treatments and diagnostics are found in in-vivo settings,
whereas applications for diagnostic use (separation/selection) are found in
vitro settings. MNPs are frequently employed in gene therapy, targeted
medication administration, electromagnetic hyperthermia, cell and macromolecule
separation, and magnetic resonance imaging (MRI). MNPs, however stand out in
particular because of their targeting capabilities. suitable for use with
medication delivery systems.
The
usage of iron oxides, and particularly magnetite, has been allowed by the Food
and Drug Administration (FDA), which has also affirmed that these materials are
completely safe for use by people. Health care has a lot of promise for
nano-based medication delivery systems. Since their size enables for
distribution through injection or other means, they offer higher drug
penetration into the body. Nanoscience is being used in medicine to enhance the
current approaches to treating certain conditions. A variety of active components
targeted to lipid disorders, atherosclerosis-related angiogenesis,
inflammation, and thrombosis prevention, among other ailments, may be delivered
through controlled drug delivery systems using nanotechnology efficiently and
securely. The development of iron oxide super-paramagnetic nanoparticles in
magnetic drug targeting has been significant. The magnetic drug targeted system
offers suitable magnetic gradients, increasing the concentration of
nanoparticles at the affected region even more .
VI.
Computational Nano-Pharmacodynamics/Nano-Hemodynamics
The
field of research known as nano-pharmacodynamics or nano-hemodynamics has
investigated several theoretical studies to demonstrate the impact of different
nanoparticles (drugs) on blood flows. Due to its relevance in the fight against
arteries with illness, stenotic nano-hemodynamics in particular has attracted a
lot of attention in the engineering sciences and applied mathematics groups.
Various computational techniques that are necessary to address the nonlinearity
of the mathematical models were highlighted in the numerous research that has
been documented. By utilising nanoparticles with a Prandtl blood flow mode and
a homotopy perturbation approach, Nadeem et al. investigated the steady blood
flow via tapered stenosed arteries. Ahmed et al. studied the effects of several
nanoparticles (Cu, TiO2, and Al2O3) on Newtonian blood flow in a single
stenosed channel and found that Al2O3 nanoparticles had a higher flow
acceleration in the core area than either Cu or TiO2 nanoparticles. Using
Buongiorno's model and the forward time central space (FTCS) approach, Ali et
al. performed a numerical simulation of the time-dependent non-Newtonian (Sisko
fluid) nano pharmacodynamic transport phenomena in an overlapping tapering
artery. The finite element technique (FEM) was used to confirm the results, and
it was discovered that the flow rate at the stenotic neck reduces as the
Brownian motion parameter rises. A robust model of non-Newtonian nanofluid
hemodynamics with heat and mass diffusion in a stenosed coronary artery in the
presence of a radial magnetic field has just been created by Vasu et al. To
help you comprehend the role of nano-drug diffusion in the therapy of
cardiovascular illness, we'll briefly go over some of the simulation's
specifics here (stenotic arteries). The formulation makes use of both
Buongiorno's nanoscale model and the Reiner-Rivlin second-order differential
model.
The
hemodynamic properties in this study were computed using the FreeFEM++ finite
element algorithm. As shown in Figure 6, the finite element mesh was created
using 5928 unstructured fixed triangular elements with 12177 nodes. The
automated FreeFEM++ mesh generator, which is based on the Delaunay-Voronoi
technique, was used to create the mesh.
Therefore,
the maximum magnetic and thermophoresis parameter values work together to
significantly reduce nanoparticle concentration values. Therefore, using a
weaker magnetic field and lower thermophoresis in nano-particle deployment in
stenotic blood flows may result in the opposite effect, elevation in nanoparticle
diffusion. Modern nano-biomedicine and drug delivery systems obviously benefit
from the visualisation capability of computational nanohemodynamics, which also
offers an ideal approach for maximising the effects of various nano-drugs in
clinical therapies. Other numerical approaches, such as Lattice Boltzman,
molecular dynamics, smoothed particle hydrodynamics, and boundary element
techniques, are also extremely promising in this area.
Conclusion
Along
with improvements in the distribution of prescription pharmaceuticals via novel
treatment techniques, current developments in nanomedicine have also been taken
into account in this study. The primary reason for using nanotechnology in
biomedicine is to improve the solubility, bioavailability, absorption, and
targeted and controlled release of medications. The effectiveness of
conventional pharmacological agents is significantly increased by the use of
nano-carriers formulated with dendrimers, liposomes, micelles, solid lipid
nanoparticles, gold, silver, titanium oxide, and cadmium sulphide polymeric
nanoparticles along with superparamagnetic iron oxide nanoparticles. Due to
their special qualities, magnetic drug delivery systems have great potential
for targeted and controlled distribution. In addition, this study has discussed
important developments in the application of computational and mathematical
hemodynamic models to simulate the effects of nanoparticle medication delivery
in cardiovascular disorders (stenotic arteries, aneurysms, etc.). A deeper
understanding of the underlying processes involved in nano-drug delivery is
made possible by computational nano-pharmaco/hemodynamics, which has several
benefits. In this regard, several techniques have been created, and they all
call for more research and clinical evidence to support them. Using computer
modelling approaches will significantly speed up the development of
nano-biomedicine, as well as increase safety and minimise toxicity.
References
1. Ghassemi M, Shahidian A. Nano and bio heat
transfer and fluid flow. Academic Press; 2017 Mar 15.
2. Biswas D. Blood flow models: a comparative
study. Mittal Publications; 2002.
3. Manton MJ. Low Reynolds number flow in slowly
varying axisymmetric tubes. Journal of Fluid Mechanics. 1971 Oct;49(3):451-9.
4. Friedman MH, Hutchins GM, Bargeron CB, Deters
OJ, Mark FF. Correlation between intimal thickness and fluid shear in human
arteries. Atherosclerosis. 1981 Jun 1;39(3):425-36.
5. Tripathi J, Vasu B, Gorla RS, Murthy PV, Dubey
A, Beg OA, Saikrishnan P. Progress in nano-drug delivery systems and
computational nano-pharmacodynamics. InICEMCI 2019-International Conference on
Engineering, Mathematical and Computational Intelligence 2019 Dec 23.
6. Prabhakaran D, Jeemon P, Sharma M, Roth GA,
Johnson C, Harikrishnan S, Gupta R, Pandian JD, Naik N, Roy A, Dhaliwal RS. The
changing patterns of cardiovascular diseases and their risk factors in the
states of India: the Global Burden of Disease Study 1990–2016. The Lancet
Global Health. 2018 Dec 1;6(12):e1339-51.
7. Choi SU, Eastman JA. Enhancing thermal
conductivity of fluids with nanoparticles. Argonne National Lab.(ANL), Argonne,
IL (United States); 1995 Oct 1.
8. Buongiorno, J., Convective transport
in nanofluids. ASME J. Heat Transfer, 128, 3: 240- 250, 2006.
9. Xuan Y, Roetzel W. Conceptions for heat
transfer correlation of nanofluids. International Journal of heat and Mass
transfer. 2000 Oct 1;43(19):3701-7.
10.
Tiwari AK,
Ghosh P, Sarkar J, Dahiya H, Parekh J. Numerical investigation of heat transfer
and fluid flow in plate heat exchanger using nanofluids. International Journal
of Thermal Sciences. 2014 Nov 1;85:93-103.
11.
Assa F,
Jafarizadeh-Malmiri H, Ajamein H, Vaghari H, Anarjan N, Ahmadi O, Berenjian A.
Chitosan magnetic nanoparticles for drug delivery systems. Critical reviews in
biotechnology. 2017 May 19;37(4):492-509.
12.
Sun,
T., Zhang, Y. S., Pang, B., Hyun, D. C., Yang, M., & Xia, Y. (2014).
Engineered nanoparticles for drug delivery in cancer therapy. Angewandte Chemie
International Edition, 53(46), 12320-12364.
13.
Martín
Giménez, V. M., Kassuha, D. E., & Manucha, W. (2017). Nanomedicine applied
to cardiovascular diseases: latest developments. Therapeutic advances in
cardiovascular disease, 11(4), 133-142.
14.
Radomska,
A., Leszczyszyn, J., & Radomski, M. W. (2016). The nanopharmacology and
nanotoxicology of nanomaterials: new opportunities and challenges. Adv Clin Exp
Med, 25(1), 151-162.
15.
De Villiers
MM, Aramwit P, Kwon GS, editors. Nanotechnology in drug delivery. Springer
Science & Business Media; 2008 Oct 29.
16.
Janko,
C., Dürr, S., Munoz, L.E., Magnetic drug targeting reduces the chemotherapeutic
burden on circulating leukocytes. Int J Mol Sci 2013; 14: 7341–7355.
17.
Nguyen
TKT, Leduc T, Ian R. Biomedical applications: magnetic nanoparticles. In:
Lyshevski SE, editor. Dekker Encyclopedia of Nanoscience and Nanotechnology.
3rd ed. Taylor & Francis & CRC Press; 2014. p. 1740–1743.
18.
Obermeier
A, Kuchler S, Matl FD, et al. Magnetic drug targeting as new therapeutic option
for the treatment of biomaterial infections. J Biomater Sci Polym Ed. 2012;
23:2321–2336.
19.
Nadeem,
S., Ijaz, S., & Akbar, N. S. (2013). Nanoparticle analysis for blood flow
of Prandtl fluid model with stenosis. International Nano Letters, 3(1), 35.
20.
Ahmed,
A., Nadeem, S. (2017). Shape effect of Cu-nanoparticles in unsteady flow
through curved artery with catheterized stenosis. Results in Physics, 7,
677-689.
21.
Ali,
N., Zaman A., Sajid M., Bég, Anwar O., Shamshuddin M. D. and Ali Kadir (2018),
Numerical simulation of time-dependent non-Newtonian nano-pharmacodynamic
transport phenomena in a tapered overlapping stenosed artery, Nanoscience and
Technology: An International Journal, 9, 247-282.
22.
Vasu,
B., Ankita Dubey and O. Anwar Bég (2019). Finite element analysis of non‐
Newtonian magnetohemodynamic flow conveying nanoparticles through a stenosed
coronary artery. Heat Transfer—Asian Research.
23.
C.
Sun and L.L. Munn (2008), Lattice Boltzmann simulation of blood flow in
digitized vessel networks, Comput Math Appl. 55(7): 1594–1600.
24.
S.
Safaei et al., Molecular dynamics simulations of Janus nanoparticles in a fluid
flow, Soft Matter, 15, 6742-6752.
25.
M.
Al-Saad et al. (2016). Blood flow simulation using smoothed particle
hydrodynamics, Proc. 24th UK Conference of the Association for Computational
Mechanics in Engineering 31 March – 1 April, Cardiff University, Cardiff, UK.
26.
Peng
H.M., Yang D.Q., Yang X.Y. (2007) The boundary element analysis of bloodstream
in the bifurcation deformity blood vessel. In: Computational Mechanics.
Springer, Berlin, Heidelberg, Germany.
27.
Villalba
Silva GC, Steindorff T, Silvestri Schuh R, Cardoso Flores N, Matte U. Drug
Repositioning Applied to Cardiovascular Disease in Mucopolysaccharidosis. Life.
2022 Dec 12;12(12):2085
28.
Mohammed M,
Devnarain N, Elhassan E, Govender T. Exploring the applications of hyaluronic
acid‐based nanoparticles for diagnosis and treatment of bacterial infections.
Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology. 2022
Jul;14(4):e1799.
29.
Ferreira
MP, Ranjan S, Correia AM, Mäkilä EM, Kinnunen SM, Zhang H, Shahbazi MA, Almeida
PV, Salonen JJ, Ruskoaho HJ, Airaksinen AJ. In vitro and in vivo assessment of
heart-homing porous silicon nanoparticles. Biomaterials. 2016 Jul 1;94:93-104.
30.
Cormode DP,
Skajaa T, Fayad ZA, Mulder WJ. Nanotechnology in medical imaging: probe design
and applications. Arteriosclerosis, thrombosis, and vascular biology. 2009 Jul
1;29(7):992-1000.