Effectiveness of Nanotechnology in Cardiovascular Disease Treatment
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This research proposal aims to explore the current effectiveness and trends underlying the usage of nanotechnology for the prevention, diagnosis and treatment of cardiovascular disease with an objective to understand its effect on quality of life as compared to patients receiving oral medications or invasive heart surgeries. The proposed research will be based upon the hypothesis that nanotechnology is an effective cardiovascular intervention in terms of improvement of patient’s health outcomes, mortality of life and overall quality of life as compared to traditional interventions such as oral medications or invasive heart surgeries.
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Running head: RESEARCH PROPOSAL
RESEARCH PROPOSAL: EFFECTIVENESS OF NANOTECHNOLOGY IN THE
PREVENTION, DIAGNOSIS AND TREATMENT OF CARDIOVASCULAR DISEASES
Name of the Student:
Name of the University:
Author note:
RESEARCH PROPOSAL: EFFECTIVENESS OF NANOTECHNOLOGY IN THE
PREVENTION, DIAGNOSIS AND TREATMENT OF CARDIOVASCULAR DISEASES
Name of the Student:
Name of the University:
Author note:
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1RESEARCH PROPOSAL
Abstract
Research Objective: The aim of the following research is to explore the current effectiveness
and trends underlying the usage of nanotechnology for the prevention, diagnosis and treatment of
cardiovascular disease with an objective to understand its effect on quality of life as compared to
patients receiving oral medications or invasive heart surgeries.
Background: With rising trends in obesity, lifestyle and occupational stresses and inadequate
dietary intake, rates of cardiovascular diseases are rising despite well-established treatments in
terms oral medications and invasive surgeries. Nanotechnology proves to be a promising
innovative intervention in this respect, which can improve life-threatening, atherosclerotic
conditions like thrombosis, vasoconstriction and inflammation through biologically potent
nanoparticles like dendrimers, micelles and liposomes.
Methodology: A quantitative, retrospective, cross sectional research design will be used, which
will firstly involve a survey exploring the views, opinions and standards followed by health
professionals, preferably cardiologists and heart surgeons on the usage of nanotechnology for
treatment and improving the quality of life in patients with cardiovascular ailments. Additional
data on the mortality rate of cardiovascular disease patients, across the age groups of below 40 as
well as above 40 years of age, receiving nanotechnology in comparison to open-heart surgery
will be collected.
Results: The responses obtained from the survey will be tested against the proposed hypothesis:
Nanotechnology is an effective cardiovascular treatment in the improvement of mortality rate
and quality of life in patients as compared to traditional cardiovascular interventions such as
invasive surgical procedures and oral medications.
Abstract
Research Objective: The aim of the following research is to explore the current effectiveness
and trends underlying the usage of nanotechnology for the prevention, diagnosis and treatment of
cardiovascular disease with an objective to understand its effect on quality of life as compared to
patients receiving oral medications or invasive heart surgeries.
Background: With rising trends in obesity, lifestyle and occupational stresses and inadequate
dietary intake, rates of cardiovascular diseases are rising despite well-established treatments in
terms oral medications and invasive surgeries. Nanotechnology proves to be a promising
innovative intervention in this respect, which can improve life-threatening, atherosclerotic
conditions like thrombosis, vasoconstriction and inflammation through biologically potent
nanoparticles like dendrimers, micelles and liposomes.
Methodology: A quantitative, retrospective, cross sectional research design will be used, which
will firstly involve a survey exploring the views, opinions and standards followed by health
professionals, preferably cardiologists and heart surgeons on the usage of nanotechnology for
treatment and improving the quality of life in patients with cardiovascular ailments. Additional
data on the mortality rate of cardiovascular disease patients, across the age groups of below 40 as
well as above 40 years of age, receiving nanotechnology in comparison to open-heart surgery
will be collected.
Results: The responses obtained from the survey will be tested against the proposed hypothesis:
Nanotechnology is an effective cardiovascular treatment in the improvement of mortality rate
and quality of life in patients as compared to traditional cardiovascular interventions such as
invasive surgical procedures and oral medications.
2RESEARCH PROPOSAL
Conclusion: This study will provide and insights on current trends in healthcare technology and
will pave the way for future innovation in cardiovascular treatment and improved health
outcomes in patients.
Conclusion: This study will provide and insights on current trends in healthcare technology and
will pave the way for future innovation in cardiovascular treatment and improved health
outcomes in patients.
3RESEARCH PROPOSAL
Table of Contents
Introduction..........................................................................................................................4
Rationale..............................................................................................................................6
Literature Review................................................................................................................7
Overview of Cardiovascular Diseases.............................................................................7
Need for Novel Interventions..........................................................................................8
Overview of Nanotechnology........................................................................................13
Nanotechnology and Disease Treatment.......................................................................14
Nanotechnology and Cardiovascular diseases...............................................................15
Research Limitations.....................................................................................................19
Research Value..................................................................................................................19
Methodology......................................................................................................................21
Research Design............................................................................................................21
Data Collection..............................................................................................................21
Data Analysis.................................................................................................................22
Data Variables...............................................................................................................22
Ethical Considerations...................................................................................................23
Conclusion.........................................................................................................................23
References..........................................................................................................................26
Table of Contents
Introduction..........................................................................................................................4
Rationale..............................................................................................................................6
Literature Review................................................................................................................7
Overview of Cardiovascular Diseases.............................................................................7
Need for Novel Interventions..........................................................................................8
Overview of Nanotechnology........................................................................................13
Nanotechnology and Disease Treatment.......................................................................14
Nanotechnology and Cardiovascular diseases...............................................................15
Research Limitations.....................................................................................................19
Research Value..................................................................................................................19
Methodology......................................................................................................................21
Research Design............................................................................................................21
Data Collection..............................................................................................................21
Data Analysis.................................................................................................................22
Data Variables...............................................................................................................22
Ethical Considerations...................................................................................................23
Conclusion.........................................................................................................................23
References..........................................................................................................................26
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4RESEARCH PROPOSAL
Introduction
According to the World Health Organization, an estimated 16% of the global population,
of which, 15% of women and 11% of men, are inflicted with obesity worldwide. Obesity is
caused due to a host of dietary and lifestyle factors such as occupational stress, lack of exercise
and consumption of a nutritionally imbalanced diet. Obesity, brings with it, a host of metabolic
complications such as diabetes mellitus, hypertension, cancer and cardiovascular disorders
(World Health Organization, 2019). As estimated by the World Health Organization,
approximately 17.6 million in the global population succumbed to cardiovascular complications
in the year 2016, with factors like obesity, substance abuse, inactivity and inadequate diet as the
root cause (World Health Organization, 2019). While traditional therapeutic interventions like
pharmacology and surgery continue to prevail, cardiovascular diseases are still on the rise and
are associated with long term complications in terms of daily life functionality and overall health
outcomes. There is hence a need to incorporate novel, comprehensive and robust interventions
for cardiovascular treatment, of which, nanotechnology has the potential to emerge as a
promising approach (Cooke & Atkins, 2016).
Research Aim: Hence, taking insights from the above, the aim of the following research
is to explore the current effectiveness and trends underlying the usage of nanotechnology for the
prevention, diagnosis and treatment of cardiovascular disease with an objective to understand its
effect on quality of life as compared to patients receiving oral medications or invasive heart
surgeries.
Research Objectives:The research will hence will be performed in alignment to the
following research objectives:
Introduction
According to the World Health Organization, an estimated 16% of the global population,
of which, 15% of women and 11% of men, are inflicted with obesity worldwide. Obesity is
caused due to a host of dietary and lifestyle factors such as occupational stress, lack of exercise
and consumption of a nutritionally imbalanced diet. Obesity, brings with it, a host of metabolic
complications such as diabetes mellitus, hypertension, cancer and cardiovascular disorders
(World Health Organization, 2019). As estimated by the World Health Organization,
approximately 17.6 million in the global population succumbed to cardiovascular complications
in the year 2016, with factors like obesity, substance abuse, inactivity and inadequate diet as the
root cause (World Health Organization, 2019). While traditional therapeutic interventions like
pharmacology and surgery continue to prevail, cardiovascular diseases are still on the rise and
are associated with long term complications in terms of daily life functionality and overall health
outcomes. There is hence a need to incorporate novel, comprehensive and robust interventions
for cardiovascular treatment, of which, nanotechnology has the potential to emerge as a
promising approach (Cooke & Atkins, 2016).
Research Aim: Hence, taking insights from the above, the aim of the following research
is to explore the current effectiveness and trends underlying the usage of nanotechnology for the
prevention, diagnosis and treatment of cardiovascular disease with an objective to understand its
effect on quality of life as compared to patients receiving oral medications or invasive heart
surgeries.
Research Objectives:The research will hence will be performed in alignment to the
following research objectives:
5RESEARCH PROPOSAL
1. To explore the current trends and opinions among health professionals on the
effectiveness of nanotechnology in improving patient health outcomes as compared to
traditional interventions such as oral medications or invasive heart surgeries.
2. To explore the effectiveness of nanotechnology in improving the quality of life in cardiac
patients in comparison to traditional interventions such as oral medications or invasive
heart surgeries.
3. To explore the effectiveness of nanotechnology in improving the mortality rate of cardiac
patients in comparison to patients receiving traditional interventions such as oral
medications or invasive heart surgeries.
Hence, taking insights from the above, the proposed research will be based upon the
following hypothesis:
1. Alternative hypothesis: Nanotechnology is an effective cardiovascular intervention in
terms of improvement of patient’s health outcomes, mortality of life and overall quality
of life as compared to traditional interventions such as oral medications or invasive heart
surgeries.
2. Null hypothesis: Nanotechnology is not an effective cardiovascular intervention in terms
of improvement of patient’s health outcomes, mortality of life and overall quality of life
as compared to traditional interventions such as oral medications or invasive heart
surgeries.
1. To explore the current trends and opinions among health professionals on the
effectiveness of nanotechnology in improving patient health outcomes as compared to
traditional interventions such as oral medications or invasive heart surgeries.
2. To explore the effectiveness of nanotechnology in improving the quality of life in cardiac
patients in comparison to traditional interventions such as oral medications or invasive
heart surgeries.
3. To explore the effectiveness of nanotechnology in improving the mortality rate of cardiac
patients in comparison to patients receiving traditional interventions such as oral
medications or invasive heart surgeries.
Hence, taking insights from the above, the proposed research will be based upon the
following hypothesis:
1. Alternative hypothesis: Nanotechnology is an effective cardiovascular intervention in
terms of improvement of patient’s health outcomes, mortality of life and overall quality
of life as compared to traditional interventions such as oral medications or invasive heart
surgeries.
2. Null hypothesis: Nanotechnology is not an effective cardiovascular intervention in terms
of improvement of patient’s health outcomes, mortality of life and overall quality of life
as compared to traditional interventions such as oral medications or invasive heart
surgeries.
6RESEARCH PROPOSAL
Rationale
At present, alteration of behavioral risk factors such as substance abuse, unhealthy diet
and sedentary lifestyle, continue to be one of the most recommended therapeutic interventions in
addition to surgery and pharmacology (Balakumar, Maung-U & Jagadeesh, 2016). With
increased globalization and technological advancement, global citizens now possess greater
accessibility and exposure to such health educational resources. However, with rising needs for
convenience, time constraints in daily routine coupled with a media culture of advertising
processed, packaged foods, such behavioral trends are increasingly becoming difficult to
mitigate among individuals (Vaidya & Gupta, V2015). Despite growing awareness on the
association between lifestyle, diet and cardiovascular disease, the prevalence of obesity,
engagement in physical inactivity and consumption of an unhealthy diet are continuing to rise
resulting in greater incidences of cardiovascular disorders – rendering traditional cardiovascular
interventions like pharmacology and invasive surgeries ineffective (Karimi et al., 2016).
Additionally, common pharmacological interventions such as statin therapy and dual anti-platelet
therapy have been implicated to yield adverse health consequences such as internal hemorrhages,
damage to the muscular and hepatic tissues loss of memory and increased rates of hyperglycemia
or diabetes mellitus (Berwanger et al., 2015). Additionally, open heart surgeries, due to their
invasive nature, have the potential to cause long term complications like infections in the chest
wound, arrhythmia, loss of memory, fever and increased risk of stroke, thrombosis and
hemorrhages in the future (Jafri et al., 2017). Hence, the inefficiencies of traditional
cardiovascular treatments and need for alternatives form one pf the underlying rationales for this
research proposal. There is hence a need to incorporate novel interventions which can improve
long term health outcomes in cardiovascular patients (Prajnamitra et al., 2019). Nanotechnology
Rationale
At present, alteration of behavioral risk factors such as substance abuse, unhealthy diet
and sedentary lifestyle, continue to be one of the most recommended therapeutic interventions in
addition to surgery and pharmacology (Balakumar, Maung-U & Jagadeesh, 2016). With
increased globalization and technological advancement, global citizens now possess greater
accessibility and exposure to such health educational resources. However, with rising needs for
convenience, time constraints in daily routine coupled with a media culture of advertising
processed, packaged foods, such behavioral trends are increasingly becoming difficult to
mitigate among individuals (Vaidya & Gupta, V2015). Despite growing awareness on the
association between lifestyle, diet and cardiovascular disease, the prevalence of obesity,
engagement in physical inactivity and consumption of an unhealthy diet are continuing to rise
resulting in greater incidences of cardiovascular disorders – rendering traditional cardiovascular
interventions like pharmacology and invasive surgeries ineffective (Karimi et al., 2016).
Additionally, common pharmacological interventions such as statin therapy and dual anti-platelet
therapy have been implicated to yield adverse health consequences such as internal hemorrhages,
damage to the muscular and hepatic tissues loss of memory and increased rates of hyperglycemia
or diabetes mellitus (Berwanger et al., 2015). Additionally, open heart surgeries, due to their
invasive nature, have the potential to cause long term complications like infections in the chest
wound, arrhythmia, loss of memory, fever and increased risk of stroke, thrombosis and
hemorrhages in the future (Jafri et al., 2017). Hence, the inefficiencies of traditional
cardiovascular treatments and need for alternatives form one pf the underlying rationales for this
research proposal. There is hence a need to incorporate novel interventions which can improve
long term health outcomes in cardiovascular patients (Prajnamitra et al., 2019). Nanotechnology
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7RESEARCH PROPOSAL
proves to be a promising innovative intervention in this respect, which can improve life-
threatening, atherosclerotic conditions like thrombosis, vasoconstriction and inflammation
through biologically potent nanoparticles like dendrimers, micelles and liposomes (Chandarana,
Curtis& Hoskins, 2018).
There is currently limited evidence on the effectiveness of nanotechnology and its
recommended standards based upon which treatment can be provided to cardiovascular patients.
The promising potential and lack of adequate evidence hence forms the underlying rationale for
conducting research on exploration of current trends of usage and effectiveness of
nanotechnology in improving health outcomes, mortality rates and quality of life in
cardiovascular patient as compared to traditional cardiovascular interventions such as oral
medications and invasive surgeries (Lakshmanan & Maulik, 2018).
Hence, based on this rationale, the following research proposal will hence provide an
outline for a research study, exploring the existing clinical opinion and awareness on the future
scope of nanotechnology in cardiovascular disease treatment and its impact on improving long
term health outcomes in patients suffering from such disorders.
Literature Review
Overview of Cardiovascular Diseases
According to the World Health Organization (WHO), cardiovascular diseases is an
umbrella term defining a group of diseases associated with the malfunctioning of the blood
vessels and the heart and are comprised of conditions such as, coronary heart disease, cerebro-
proves to be a promising innovative intervention in this respect, which can improve life-
threatening, atherosclerotic conditions like thrombosis, vasoconstriction and inflammation
through biologically potent nanoparticles like dendrimers, micelles and liposomes (Chandarana,
Curtis& Hoskins, 2018).
There is currently limited evidence on the effectiveness of nanotechnology and its
recommended standards based upon which treatment can be provided to cardiovascular patients.
The promising potential and lack of adequate evidence hence forms the underlying rationale for
conducting research on exploration of current trends of usage and effectiveness of
nanotechnology in improving health outcomes, mortality rates and quality of life in
cardiovascular patient as compared to traditional cardiovascular interventions such as oral
medications and invasive surgeries (Lakshmanan & Maulik, 2018).
Hence, based on this rationale, the following research proposal will hence provide an
outline for a research study, exploring the existing clinical opinion and awareness on the future
scope of nanotechnology in cardiovascular disease treatment and its impact on improving long
term health outcomes in patients suffering from such disorders.
Literature Review
Overview of Cardiovascular Diseases
According to the World Health Organization (WHO), cardiovascular diseases is an
umbrella term defining a group of diseases associated with the malfunctioning of the blood
vessels and the heart and are comprised of conditions such as, coronary heart disease, cerebro-
8RESEARCH PROPOSAL
vascular heart disease, peripheral heart disease, rheumatic heart disease, congenital heart disease,
pulmonary embolism and deep vein thrombosis (World Health Organization, 2019).
Myocardial infarction and cerebro-vascular accidents are life threatening cardiovascular
conditions that are caused due to underlying blockages across blood vessels resulting in
disruption of nutritious oxygen and nutrient rich blood to essential organs, such as the brain and
the heart, which can exert fatal consequences (Anderson& Morrow, 2017). One of the most
prevalent reasons contributing to such conditions is the deposition of fatty streaks in the
endothelium or internals walls lining the major blood vessels circulating to the brain, heart and
associated organs. Such conditions further progress into formation of large blood clots which
disrupt blood circulation and often cause a rupture across the affected area of the blood vessel,
known as a stroke, resulting in internal hemorrhages (Heusch&Gersh, 2016).
As estimated by the World Health Organization (WHO), cardiovascular diseases (CVD)
comprise of one of the leading causes of death as the highest contributor of mortality in the
global population. In the year 2016, it was estimated that CVDs were the cause of death for a
total of 17.9 million in the world, which comprises of 31% worldwide deaths. Out of this
percentage, stroke and heart attacks are considered to be contributors of approximately 85% of
deaths due to CVD in the world (World Health Organization, 2019).
Need for Novel Interventions
According to the World Health Organization (WHO), several behavioral aspects are some
of the key risk factors underlying the occurrence of CVDs. These include obesity and overweight
anthropometric conditions, consumption of processed foods or a diet rich in salt, saturated fats
and sugar and substance use such as smoking and intake of alcohol. Reducing or regulating the
vascular heart disease, peripheral heart disease, rheumatic heart disease, congenital heart disease,
pulmonary embolism and deep vein thrombosis (World Health Organization, 2019).
Myocardial infarction and cerebro-vascular accidents are life threatening cardiovascular
conditions that are caused due to underlying blockages across blood vessels resulting in
disruption of nutritious oxygen and nutrient rich blood to essential organs, such as the brain and
the heart, which can exert fatal consequences (Anderson& Morrow, 2017). One of the most
prevalent reasons contributing to such conditions is the deposition of fatty streaks in the
endothelium or internals walls lining the major blood vessels circulating to the brain, heart and
associated organs. Such conditions further progress into formation of large blood clots which
disrupt blood circulation and often cause a rupture across the affected area of the blood vessel,
known as a stroke, resulting in internal hemorrhages (Heusch&Gersh, 2016).
As estimated by the World Health Organization (WHO), cardiovascular diseases (CVD)
comprise of one of the leading causes of death as the highest contributor of mortality in the
global population. In the year 2016, it was estimated that CVDs were the cause of death for a
total of 17.9 million in the world, which comprises of 31% worldwide deaths. Out of this
percentage, stroke and heart attacks are considered to be contributors of approximately 85% of
deaths due to CVD in the world (World Health Organization, 2019).
Need for Novel Interventions
According to the World Health Organization (WHO), several behavioral aspects are some
of the key risk factors underlying the occurrence of CVDs. These include obesity and overweight
anthropometric conditions, consumption of processed foods or a diet rich in salt, saturated fats
and sugar and substance use such as smoking and intake of alcohol. Reducing or regulating the
9RESEARCH PROPOSAL
adherence to such risk factors is one of the most prevalent ways of reducing the risk of CVDs
across individuals (World Health Organization, 2019). However, despite considerable awareness
concerning the need to avoid such behaviors, trends in the consumption of unhealthy diets and
lack of exercise continue to aggravate hence resulting in the need to administer more robust
interventions for the treatment and management of CVDs (Hulsegge et al., 2016).
At present, as researched by Elmariah et al., (2018), the current therapeutic interventions
underlying the treatment and management of CVDs, in addition to behavioral change, includes
pharmacological interventions and surgical methods such as invasive heart surgeries. Behavioral
risk factors continue to remain difficult to reverse due to occupational stresses and increased
marketing and advertisement of processed foods. Additionally, pharmacological interventions
also possess uncertainties in case of efficiency, as evidenced by low response of individuals who
have already encountered an episode of acute myocardial infarction, towards clopidogrel – a
medication administered for the reduction of CVDs and strokes especially after incidences of
heart attacks or surgical placements such as coronary stents.
Alternative interventions for CVDs include invasive surgeries such as open heart or
coronary bypass grafting methods, which may not be tolerated by some individuals (especially
those with multiple metabolicsymptoms like diabetes and hypertension) and result in long
termcomplications in the form of infections in the chest wounds, recurrent fever and perceptions
of pain, damage to additional organs such as renal or pulmonary failure, loss of memory and
blood or relapse of cardiovascular symptoms such as clot formation and possibilities of stroke
and myocardial infarction (Hassan et al., 2018).Such adversities associated with traditional
interventions of CVD treatment hence necessitates the need to administer alternative therapeutic
technologies which are not only minimally invasive and hence, devoid of the complications
adherence to such risk factors is one of the most prevalent ways of reducing the risk of CVDs
across individuals (World Health Organization, 2019). However, despite considerable awareness
concerning the need to avoid such behaviors, trends in the consumption of unhealthy diets and
lack of exercise continue to aggravate hence resulting in the need to administer more robust
interventions for the treatment and management of CVDs (Hulsegge et al., 2016).
At present, as researched by Elmariah et al., (2018), the current therapeutic interventions
underlying the treatment and management of CVDs, in addition to behavioral change, includes
pharmacological interventions and surgical methods such as invasive heart surgeries. Behavioral
risk factors continue to remain difficult to reverse due to occupational stresses and increased
marketing and advertisement of processed foods. Additionally, pharmacological interventions
also possess uncertainties in case of efficiency, as evidenced by low response of individuals who
have already encountered an episode of acute myocardial infarction, towards clopidogrel – a
medication administered for the reduction of CVDs and strokes especially after incidences of
heart attacks or surgical placements such as coronary stents.
Alternative interventions for CVDs include invasive surgeries such as open heart or
coronary bypass grafting methods, which may not be tolerated by some individuals (especially
those with multiple metabolicsymptoms like diabetes and hypertension) and result in long
termcomplications in the form of infections in the chest wounds, recurrent fever and perceptions
of pain, damage to additional organs such as renal or pulmonary failure, loss of memory and
blood or relapse of cardiovascular symptoms such as clot formation and possibilities of stroke
and myocardial infarction (Hassan et al., 2018).Such adversities associated with traditional
interventions of CVD treatment hence necessitates the need to administer alternative therapeutic
technologies which are not only minimally invasive and hence, devoid of the complications
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10RESEARCH PROPOSAL
associated with invasive surgeries, but will also be of optimum potency for the alleviation of
symptoms associated with CVDs (Sharma et al., 2016).
One of the most prevalent conditions which are associated with high mortality due to
CVDs, is ischemia and myocardial infarction. An underlying CVD pathology which is
responsible for these conditions is atherosclerosis. Atherosclerosis is caused due to accumulation
excessive deposition and accumulation of cholesterol, macrophage cells, cholesterol and fat in
the endothelial lining of blood vessels resulting in their hardening to form plaques in the future.
Such atherosclerotic depositions progress to further severe complications such as narrowed blood
vessel, blockages and disturbances in normal blood circulation, rupturing of the affected blood
vessels and hence a condition of ischemia (Lesnefsky et al., 2017). Anincident of ischemia
occurring in the cardiovascular system results in deprivation of nutrient rich blood to the heart
further leading to loss of oxygen, malfunctioning of the surrounding cardiac muscles and hence
an episode of heart attack or myocardial infarction. Compensatory mechanisms occur in the body
as a response, known as reperfusion, and are associated with an increase in the permeability of
arterioles and capillaries resulting increased rates of diffusion and filtration in the endothelial
tissues. However, ironically, such mechanisms are often followed by increased oxidative damage
resultant cell apoptosis due to the high production of reactive oxygen species in comparison to
nitric oxide by endothelial cells which are activated to exert the above reperfusion mechanisms.
Such a CVD condition is known as ischemia/ reperfusion injury (Ibanez et al., 2015).
Cardiomyocytes are the cells forming the muscular tissues of the heart and hence are the
major components responsible for the contraction required to initiate blood circulation. An
episode of myocardial infarction results in a loss of approximately 25% of these cardiac muscle
cells. Mature cardiomyocytes possess reduced ability to proliferate resulting in a permanent loss
associated with invasive surgeries, but will also be of optimum potency for the alleviation of
symptoms associated with CVDs (Sharma et al., 2016).
One of the most prevalent conditions which are associated with high mortality due to
CVDs, is ischemia and myocardial infarction. An underlying CVD pathology which is
responsible for these conditions is atherosclerosis. Atherosclerosis is caused due to accumulation
excessive deposition and accumulation of cholesterol, macrophage cells, cholesterol and fat in
the endothelial lining of blood vessels resulting in their hardening to form plaques in the future.
Such atherosclerotic depositions progress to further severe complications such as narrowed blood
vessel, blockages and disturbances in normal blood circulation, rupturing of the affected blood
vessels and hence a condition of ischemia (Lesnefsky et al., 2017). Anincident of ischemia
occurring in the cardiovascular system results in deprivation of nutrient rich blood to the heart
further leading to loss of oxygen, malfunctioning of the surrounding cardiac muscles and hence
an episode of heart attack or myocardial infarction. Compensatory mechanisms occur in the body
as a response, known as reperfusion, and are associated with an increase in the permeability of
arterioles and capillaries resulting increased rates of diffusion and filtration in the endothelial
tissues. However, ironically, such mechanisms are often followed by increased oxidative damage
resultant cell apoptosis due to the high production of reactive oxygen species in comparison to
nitric oxide by endothelial cells which are activated to exert the above reperfusion mechanisms.
Such a CVD condition is known as ischemia/ reperfusion injury (Ibanez et al., 2015).
Cardiomyocytes are the cells forming the muscular tissues of the heart and hence are the
major components responsible for the contraction required to initiate blood circulation. An
episode of myocardial infarction results in a loss of approximately 25% of these cardiac muscle
cells. Mature cardiomyocytes possess reduced ability to proliferate resulting in a permanent loss
11RESEARCH PROPOSAL
of cardiomyocytes with every incidence of a heart attack. The only mechanism with which the
heart undergoes regeneration after considerable damage is via forming fibrous scar tissue which
are incapable of exerting the contractive function which is characteristic of cardiomyocytes
(Prajnamitra et al., 2019) Such process of scar tissue deposition is known as ventricular
remodeling and is associated with increased weakening of cardiac muscles and increased burden
of circulation which the heart is required to withstand. Further progression of such conditions are
associated with a gradual decrease in the strength and contractility of cardiac muscles and overall
deterioration of the heart which may additionally increase an individual’s susceptibility to fatal
conditions like congestive heart failure and death (Westman et al., 2016).
Hence, the essential role of cardiomyocytes for the maintenance of normal functioning of
the heart is evident from the above. Present day advancements in medical technology have been
developed in alignment of the of the role of these cells, which comprise of regenerating and
grafting of cardiomyocytes in the affected regions, include induced pluripotent stem cells
(iPSCs) or derivation of embryonic stem cells (ESCs) (Columbo et al., 2018). However, such
stem cell therapies have been found to possess considerable inadequacies in the form of delayed
maturation of cardiomyocytes, issues during transplantation and complication associated with the
proliferation of malignant teratomas in the future. Alternatively, if the myocardium has not
encountered severe damages, there may be a possibility of administering therapeutic substances
which are cardioprotective in nature so that cardiomyocytes do not have to encounter any further
damages or destruction as a result of injuries like myocardial infarctions (Prajnamitra et al.,
2016).
Taking insights from the Research by Prajnamitra et al., (2019), nanotechnology poses to
be a promising innovative option for revolutionizing the field of biomedicine aim at
of cardiomyocytes with every incidence of a heart attack. The only mechanism with which the
heart undergoes regeneration after considerable damage is via forming fibrous scar tissue which
are incapable of exerting the contractive function which is characteristic of cardiomyocytes
(Prajnamitra et al., 2019) Such process of scar tissue deposition is known as ventricular
remodeling and is associated with increased weakening of cardiac muscles and increased burden
of circulation which the heart is required to withstand. Further progression of such conditions are
associated with a gradual decrease in the strength and contractility of cardiac muscles and overall
deterioration of the heart which may additionally increase an individual’s susceptibility to fatal
conditions like congestive heart failure and death (Westman et al., 2016).
Hence, the essential role of cardiomyocytes for the maintenance of normal functioning of
the heart is evident from the above. Present day advancements in medical technology have been
developed in alignment of the of the role of these cells, which comprise of regenerating and
grafting of cardiomyocytes in the affected regions, include induced pluripotent stem cells
(iPSCs) or derivation of embryonic stem cells (ESCs) (Columbo et al., 2018). However, such
stem cell therapies have been found to possess considerable inadequacies in the form of delayed
maturation of cardiomyocytes, issues during transplantation and complication associated with the
proliferation of malignant teratomas in the future. Alternatively, if the myocardium has not
encountered severe damages, there may be a possibility of administering therapeutic substances
which are cardioprotective in nature so that cardiomyocytes do not have to encounter any further
damages or destruction as a result of injuries like myocardial infarctions (Prajnamitra et al.,
2016).
Taking insights from the Research by Prajnamitra et al., (2019), nanotechnology poses to
be a promising innovative option for revolutionizing the field of biomedicine aim at
12RESEARCH PROPOSAL
cardiovascular protection through the formulation of nanoparticles and substances capable of
application in biological systems. Such nanoparticles can be used for a variety of biomedical
procedures including the treatment of disease including CVDs. The range of applications in
which nanotechnology and associated nanoparticles find their use, include the delivery of drugs,
scaffolding for modulation of stem cells, diagnostic agents used for producing in vivo images
and engineering of tissues to name a few.
Considering the disruptions in blood circulation caused due to atherosclerosis, present
day interventions for CVDs are centered on the restoration of normal circulatory processes in the
affected or damaged vascular regions in order to prevent further profession of cardiovascular
symptoms. Current interventions associated usage of statins are commonly administered with the
aim of reducing excessive accumulation and hardening of atherosclerotic plaques and alleviating
symptoms of buildup of calcium and loss of elasticity in the endothelial lining of the blood
vessels (Scheitz et al., 2016). Additional first line treatments for prevention of CVDs include the
administration of dual anti-platelet therapies comprising of P2Y12 inhibitors like clopidogrel and
inhibitors of cyclooxygenases such as aspirin. Such interventions are aimed at ensuring
reductions in the formation of clots and aggregation of platelets. Despite the prevalent and
popular usage of such treatments, there is a need for further improvement, since interventions
like anti-platelet therapies are associated reduced rates of compliance among patients and
adverse consequences such as hemorrhages and internal organ bleeding (Dadjou, Safavi&Kojuri,
2016). Further, positive effects and alleviation of CVD symptoms have not been observed in
every patient and hence raised doubts on the possibilities of acquiring long term complications in
patients receiving dual anti-platelet therapy. There have been additional reports indicating that
patients who have already suffered from an incident of heart attack, generally demonstrate
cardiovascular protection through the formulation of nanoparticles and substances capable of
application in biological systems. Such nanoparticles can be used for a variety of biomedical
procedures including the treatment of disease including CVDs. The range of applications in
which nanotechnology and associated nanoparticles find their use, include the delivery of drugs,
scaffolding for modulation of stem cells, diagnostic agents used for producing in vivo images
and engineering of tissues to name a few.
Considering the disruptions in blood circulation caused due to atherosclerosis, present
day interventions for CVDs are centered on the restoration of normal circulatory processes in the
affected or damaged vascular regions in order to prevent further profession of cardiovascular
symptoms. Current interventions associated usage of statins are commonly administered with the
aim of reducing excessive accumulation and hardening of atherosclerotic plaques and alleviating
symptoms of buildup of calcium and loss of elasticity in the endothelial lining of the blood
vessels (Scheitz et al., 2016). Additional first line treatments for prevention of CVDs include the
administration of dual anti-platelet therapies comprising of P2Y12 inhibitors like clopidogrel and
inhibitors of cyclooxygenases such as aspirin. Such interventions are aimed at ensuring
reductions in the formation of clots and aggregation of platelets. Despite the prevalent and
popular usage of such treatments, there is a need for further improvement, since interventions
like anti-platelet therapies are associated reduced rates of compliance among patients and
adverse consequences such as hemorrhages and internal organ bleeding (Dadjou, Safavi&Kojuri,
2016). Further, positive effects and alleviation of CVD symptoms have not been observed in
every patient and hence raised doubts on the possibilities of acquiring long term complications in
patients receiving dual anti-platelet therapy. There have been additional reports indicating that
patients who have already suffered from an incident of heart attack, generally demonstrate
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13RESEARCH PROPOSAL
reduced rates of responses towards dual anti-platelet therapy medications and a high
susceptibility of projecting recurrent events of CVDs in the future or during phases of follow up.
Such adversities, hence strengthen the need to administer more advanced fields of therapeutic
interventions, of which, nanotechnology has the potential to be an effective alternative
(Prajnamitra et al., 2019).
Overview of Nanotechnology
Nanotechnology can be defined as a novel and innovative field of molecular science that
comprises of usage and manipulation of substances and equipment at the supra-molecular,
molecular and atomic level, that is, at the nano scale. In terms of scalability, the measurement of
a nanometer can be estimated at 1, 80, 000 of strand of human hair or 10 times the diameter
found in hydrogen atoms. One of the first definitions of nanotechnology, defined it as a field of
technology aimed at manipulation of molecule and atoms for the formulation of products at the
overall macroscale level – a subject which is now known by the name of ‘molecular
biotechnology’ (Kuzmov & Minko, 2015). Further, a more generalized yet comprehensive
definition was postulated by the National Nanotechnology Initiative, which described
nanotechnology as a field concerned with manipulating matter at a minimum of one dimension
ranging from 1 to 100 nanometers. Such a of nanotechnology is reflective of the important role
processes of quantum mechanics for the optimum application of nanotechnology hence resulting
in a shift of description from a technological aspect to a subject of research which comprises of
all forms of technologies, innovations and research which are dealing with matter occurring at a
level less than the above mentioned threshold (Jurj et al., 2017).
Overall, as researched by Savaliya et al., (2015), nanotechnology as a subject, has been
considered as expansive and broad and hence, finds application in a wide range of fields, such as
reduced rates of responses towards dual anti-platelet therapy medications and a high
susceptibility of projecting recurrent events of CVDs in the future or during phases of follow up.
Such adversities, hence strengthen the need to administer more advanced fields of therapeutic
interventions, of which, nanotechnology has the potential to be an effective alternative
(Prajnamitra et al., 2019).
Overview of Nanotechnology
Nanotechnology can be defined as a novel and innovative field of molecular science that
comprises of usage and manipulation of substances and equipment at the supra-molecular,
molecular and atomic level, that is, at the nano scale. In terms of scalability, the measurement of
a nanometer can be estimated at 1, 80, 000 of strand of human hair or 10 times the diameter
found in hydrogen atoms. One of the first definitions of nanotechnology, defined it as a field of
technology aimed at manipulation of molecule and atoms for the formulation of products at the
overall macroscale level – a subject which is now known by the name of ‘molecular
biotechnology’ (Kuzmov & Minko, 2015). Further, a more generalized yet comprehensive
definition was postulated by the National Nanotechnology Initiative, which described
nanotechnology as a field concerned with manipulating matter at a minimum of one dimension
ranging from 1 to 100 nanometers. Such a of nanotechnology is reflective of the important role
processes of quantum mechanics for the optimum application of nanotechnology hence resulting
in a shift of description from a technological aspect to a subject of research which comprises of
all forms of technologies, innovations and research which are dealing with matter occurring at a
level less than the above mentioned threshold (Jurj et al., 2017).
Overall, as researched by Savaliya et al., (2015), nanotechnology as a subject, has been
considered as expansive and broad and hence, finds application in a wide range of fields, such as
14RESEARCH PROPOSAL
molecular biology, semiconductor physics, organic chemistry, microfabrication, surface science
and molecular engineering. The research, potential application and usage of conceptsemerging
from nanotechnology are also diverse and have been found to be include primarily: the
development of novel substances at nanoscale dimensions, assembling and dismantling of
existing molecular structures of substances, alteration of the existing physics driving substances
and devices and controlling or manipulating the matter of substances at their atomic or molecular
levels.
Despite the potential scope and advantages of such innovations, the field of
nanotechnology also undergoes speculation in terms of its validity, credibility and potential
safety or risks underlying the future of its application. At present, nanotechnology is considered
for application across a variety of fields, namely, nanoelectronics, nanomedicine and production
of biomaterials for industrial as well as commercial purposes (Rahi, Sattarahmady& Heli, 2015).
However, similar to the application of any other technology, product of innovation, the usage of
nanotechnology has also raised several concerns such as its environmental sustainability and
economicalimpact, as well as its recommended levels of safety and toxicity. Such speculations
have hence resulted in considerable debate and discussion between governmental bodies,
international organizations as well as advocacy groups on the need to standardize or regulate the
application of nanotechnology, especially in health and medical fields (Jain, Kumar Mehra&
Jain, 2015).
Nanotechnology and Disease Treatment
Nanomedicines is field associated with the production of therapeutic nanoparticles aimed
at diagnosing, treating and preventing injuries and diseases for improving and maintaining
optimum levels of health and wellbeing in individuals. A key example of this is a field of
molecular biology, semiconductor physics, organic chemistry, microfabrication, surface science
and molecular engineering. The research, potential application and usage of conceptsemerging
from nanotechnology are also diverse and have been found to be include primarily: the
development of novel substances at nanoscale dimensions, assembling and dismantling of
existing molecular structures of substances, alteration of the existing physics driving substances
and devices and controlling or manipulating the matter of substances at their atomic or molecular
levels.
Despite the potential scope and advantages of such innovations, the field of
nanotechnology also undergoes speculation in terms of its validity, credibility and potential
safety or risks underlying the future of its application. At present, nanotechnology is considered
for application across a variety of fields, namely, nanoelectronics, nanomedicine and production
of biomaterials for industrial as well as commercial purposes (Rahi, Sattarahmady& Heli, 2015).
However, similar to the application of any other technology, product of innovation, the usage of
nanotechnology has also raised several concerns such as its environmental sustainability and
economicalimpact, as well as its recommended levels of safety and toxicity. Such speculations
have hence resulted in considerable debate and discussion between governmental bodies,
international organizations as well as advocacy groups on the need to standardize or regulate the
application of nanotechnology, especially in health and medical fields (Jain, Kumar Mehra&
Jain, 2015).
Nanotechnology and Disease Treatment
Nanomedicines is field associated with the production of therapeutic nanoparticles aimed
at diagnosing, treating and preventing injuries and diseases for improving and maintaining
optimum levels of health and wellbeing in individuals. A key example of this is a field of
15RESEARCH PROPOSAL
nanomedicine with ability of manipulating supramolecular and biomacromolecular substances
necessary for life, and is inclusive of plasma membranes, RNA, DNA and bilayers of lipids.
Nanoparticles produced with therapeutic functions, have been postulated to possess
physiochemical attributes which are beneficial for biological functioning such as high levels of
surface energy as a result of their high amounts of reactivity, wettability, roughness and ratio of
surface area to volume (Singh, 2016). Additional innovations in this field include the
modification of the properties of a substance at the nanoparticle level while simultaneously
maintaining the biological compatibility of the substance. Such innovations find use in a variety
of applications such as reduction of toxicity, enhancement of the half-life of pharmaceuticals and
reduction of side effects (Maher, 2018). A major application for which nanoparticle usage is
considered to be exclusively effective is the targeted delivery of drugs via both active as well as
passive method, for the purpose of disease treatment. Active targeted delivery of drugs
comprises of conjugating the therapeutic nanoparticle to a ligand specific to tissues and cells
while passives means of targeted drug delivery comprises of coupling between the therapeutic
nanoparticle and a polymer of high molecular weight resulting increased rates of permeability
and retention capacities in vascular and endothelial tissues (Cooke & Atkins, 2016).
Nanotechnology and Cardiovascular diseases
At present, as researched by Chandarana, Curtis and Hoskins (2018),nanotechnology has
contributed to the production of wide range of nanoparticles with medicinal properties, that is,
nanomedicines. Each nanoparticle possesses its own diverse set of benefits and properties and
include liposomes, micelles, nanoparticles, dendrimers and nano-coatings. Present day medicinal
application of nanotechnology are generally focused around management and treatment of
cancer. However, with rising trends of disease prevalence – this innovative field is undergoing
nanomedicine with ability of manipulating supramolecular and biomacromolecular substances
necessary for life, and is inclusive of plasma membranes, RNA, DNA and bilayers of lipids.
Nanoparticles produced with therapeutic functions, have been postulated to possess
physiochemical attributes which are beneficial for biological functioning such as high levels of
surface energy as a result of their high amounts of reactivity, wettability, roughness and ratio of
surface area to volume (Singh, 2016). Additional innovations in this field include the
modification of the properties of a substance at the nanoparticle level while simultaneously
maintaining the biological compatibility of the substance. Such innovations find use in a variety
of applications such as reduction of toxicity, enhancement of the half-life of pharmaceuticals and
reduction of side effects (Maher, 2018). A major application for which nanoparticle usage is
considered to be exclusively effective is the targeted delivery of drugs via both active as well as
passive method, for the purpose of disease treatment. Active targeted delivery of drugs
comprises of conjugating the therapeutic nanoparticle to a ligand specific to tissues and cells
while passives means of targeted drug delivery comprises of coupling between the therapeutic
nanoparticle and a polymer of high molecular weight resulting increased rates of permeability
and retention capacities in vascular and endothelial tissues (Cooke & Atkins, 2016).
Nanotechnology and Cardiovascular diseases
At present, as researched by Chandarana, Curtis and Hoskins (2018),nanotechnology has
contributed to the production of wide range of nanoparticles with medicinal properties, that is,
nanomedicines. Each nanoparticle possesses its own diverse set of benefits and properties and
include liposomes, micelles, nanoparticles, dendrimers and nano-coatings. Present day medicinal
application of nanotechnology are generally focused around management and treatment of
cancer. However, with rising trends of disease prevalence – this innovative field is undergoing
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16RESEARCH PROPOSAL
rapid expansion to include production of treatment alternatives for cardiovascular disease and
resistance towards antibiotics. At present, the following research proposal will aim to expand
upon the most traditionally used and widely prevalent nanomedicines with potential for cardio-
protection, which are, liposomes, micelles and dendrimers.
Table 1: Summary of nanotechnology applications in cardiovascular disease (Source:
Chandarana, M., Curtis, A., & Hoskins, C. (2018). The use of nanotechnology in cardiovascular
disease. Applied Nanoscience, 8(7), 1607-1619.
Class Application
Liposome Thrombosis, Atherosclerosis, Vasodilation,
Cardio-protectant
Polymeric Nanoparticle Thrombosis, Atherosclerosis, Cardio-
protectant
Polymeric micelle Thrombosis, Atherosclerosis, Vasodilation,
Cardio-protectant
Dendrimer Thrombosis, Atherosclerosis, Vasodilation,
Cardio-protectant
Gelated Nanoparticle Cardio-protectant
Nano-coating Biocompatibility of implants
Liposomes are nanoparticles with an ability to form structures with bilayer of
phospholipid, at a size approximately 50 to 200 nm. These lipid layer encapsulate within
themselves a core of aqueous solutions, containing substances such as cholesterol. Liposomes are
effective substances for the purpose of targeted delivery of drugs due to them possessing both
hydrophophic and hydrophilic qualities (Matoba et al., 2017). Taking insights from the same,
liposomes with cores of urokinase – a drug with thrombolytic properties – have been designed
for the purpose of treatment of thrombolysis, using targeted delivery of drugs. An additional
substance which has been evidenced to be an effective cardio-protectant, is berberine, which
when encapsulated within loposomes, have been found to improve functioning of heart against
rapid expansion to include production of treatment alternatives for cardiovascular disease and
resistance towards antibiotics. At present, the following research proposal will aim to expand
upon the most traditionally used and widely prevalent nanomedicines with potential for cardio-
protection, which are, liposomes, micelles and dendrimers.
Table 1: Summary of nanotechnology applications in cardiovascular disease (Source:
Chandarana, M., Curtis, A., & Hoskins, C. (2018). The use of nanotechnology in cardiovascular
disease. Applied Nanoscience, 8(7), 1607-1619.
Class Application
Liposome Thrombosis, Atherosclerosis, Vasodilation,
Cardio-protectant
Polymeric Nanoparticle Thrombosis, Atherosclerosis, Cardio-
protectant
Polymeric micelle Thrombosis, Atherosclerosis, Vasodilation,
Cardio-protectant
Dendrimer Thrombosis, Atherosclerosis, Vasodilation,
Cardio-protectant
Gelated Nanoparticle Cardio-protectant
Nano-coating Biocompatibility of implants
Liposomes are nanoparticles with an ability to form structures with bilayer of
phospholipid, at a size approximately 50 to 200 nm. These lipid layer encapsulate within
themselves a core of aqueous solutions, containing substances such as cholesterol. Liposomes are
effective substances for the purpose of targeted delivery of drugs due to them possessing both
hydrophophic and hydrophilic qualities (Matoba et al., 2017). Taking insights from the same,
liposomes with cores of urokinase – a drug with thrombolytic properties – have been designed
for the purpose of treatment of thrombolysis, using targeted delivery of drugs. An additional
substance which has been evidenced to be an effective cardio-protectant, is berberine, which
when encapsulated within loposomes, have been found to improve functioning of heart against
17RESEARCH PROPOSAL
processes of ventricular remodeling and reduce the secretion of pro-inflammatory interleukin 6
(Allijn et al., 2017). The phospholipid layer of liposomescn further be manipulated to include a
wide variety of medicinal propeorties adding polyethylene glycol (PEG) to the surface of
liposomes renders a range of beneficial properties such as extended time for circulation,
reduction in uptake and reduction in time taken by the liver or phagocytes for clearance. For
further targeted delivery, the liposomal surface layers can be attached with antibodies. There is
however, a need further research to combat some of the disadvantages of drug delivery processes
by liposomes, which include: structural instability resulting in release of drugs in a much
premature stage (Chandarana, Curtis & Hoskins, 2018)
Figure 1: Usage of nanoparticles for treatment of ischemia induced cardiac injuries: A: Passive and
active drug delivery targeting using enhanced permeability and retention (EPR) effect and
nanoparticles with targeting moieties, B: Distribution of nanoparticles in biological systems to
understand their fat when administered in-vivo. (Source: Prajnamitra, R. P., Chen, H. C., Lin, C. J.,
Chen, L. L., & Hsieh, P. C. H. (2019). Nanotechnology Approaches in Tackling Cardiovascular
Diseases. Molecules, 24(10), 2017.
processes of ventricular remodeling and reduce the secretion of pro-inflammatory interleukin 6
(Allijn et al., 2017). The phospholipid layer of liposomescn further be manipulated to include a
wide variety of medicinal propeorties adding polyethylene glycol (PEG) to the surface of
liposomes renders a range of beneficial properties such as extended time for circulation,
reduction in uptake and reduction in time taken by the liver or phagocytes for clearance. For
further targeted delivery, the liposomal surface layers can be attached with antibodies. There is
however, a need further research to combat some of the disadvantages of drug delivery processes
by liposomes, which include: structural instability resulting in release of drugs in a much
premature stage (Chandarana, Curtis & Hoskins, 2018)
Figure 1: Usage of nanoparticles for treatment of ischemia induced cardiac injuries: A: Passive and
active drug delivery targeting using enhanced permeability and retention (EPR) effect and
nanoparticles with targeting moieties, B: Distribution of nanoparticles in biological systems to
understand their fat when administered in-vivo. (Source: Prajnamitra, R. P., Chen, H. C., Lin, C. J.,
Chen, L. L., & Hsieh, P. C. H. (2019). Nanotechnology Approaches in Tackling Cardiovascular
Diseases. Molecules, 24(10), 2017.
18RESEARCH PROPOSAL
As researched by Luan and Zhai (2016), micelles are another type of nanomedicine
possessing structures which are amphiphillic. Micelles have shells which are hydrophilic
properties and cores which are hydrophobic. These medicinal nanoparticles possess such
properties since they are prepared using lipid or polymer based molecules with amphiphillic
properties. Similar to the properties of liposomes, micelles possess the ability of encapsulating
and carrying drugs due to the hydrophobic properties present in their core, as well improved for
systemic exposure and circulation time due to their hydrophilic shell structure. Additionally, as
researched by Vong et al., (2018), the small size of micelles also render them the property to
overcome membrane and exert therapeutic action on the affected cardiac tissues. The
formulation of micelles with structures of copolymers of methoxy polyethylene glycol have been
found to be effective for the encapsulation of lumbrokinase and in administering thrombolytic
effects for alleviating symptoms of thrombosis. Further, as postulated by Chandarana, Curtis and
(2018), cardio-protective micelles which have undergone development is the encapsulation of
andrographolide, a compound derived from plants, which when delivered using micelles
structured using polypropylene sulphides and polyethylene glycol have been found to be
effective in the treatment of atherosclerosis, reduction of inflammatory reactive oxygen species
and enhanced regulation of endothelial nitric oxide and hence the resultant decrease in the action
of pro-inflammatory cytokines.
Dendrimers are implicated to be the most uniquely structured nanomedicines. The
structure of dendrimers comprise of three dimensional stems with multiple branches. Dendrimers
are considered excellent carriers for targeted delivery of drugs due their structure which grants
them a range of advantages such as: enhances stability, increased rates of solubility and minimal
immunogenic properties (Gothwal et al., 2015). Encapsulation of nitric oxide - a compound with
As researched by Luan and Zhai (2016), micelles are another type of nanomedicine
possessing structures which are amphiphillic. Micelles have shells which are hydrophilic
properties and cores which are hydrophobic. These medicinal nanoparticles possess such
properties since they are prepared using lipid or polymer based molecules with amphiphillic
properties. Similar to the properties of liposomes, micelles possess the ability of encapsulating
and carrying drugs due to the hydrophobic properties present in their core, as well improved for
systemic exposure and circulation time due to their hydrophilic shell structure. Additionally, as
researched by Vong et al., (2018), the small size of micelles also render them the property to
overcome membrane and exert therapeutic action on the affected cardiac tissues. The
formulation of micelles with structures of copolymers of methoxy polyethylene glycol have been
found to be effective for the encapsulation of lumbrokinase and in administering thrombolytic
effects for alleviating symptoms of thrombosis. Further, as postulated by Chandarana, Curtis and
(2018), cardio-protective micelles which have undergone development is the encapsulation of
andrographolide, a compound derived from plants, which when delivered using micelles
structured using polypropylene sulphides and polyethylene glycol have been found to be
effective in the treatment of atherosclerosis, reduction of inflammatory reactive oxygen species
and enhanced regulation of endothelial nitric oxide and hence the resultant decrease in the action
of pro-inflammatory cytokines.
Dendrimers are implicated to be the most uniquely structured nanomedicines. The
structure of dendrimers comprise of three dimensional stems with multiple branches. Dendrimers
are considered excellent carriers for targeted delivery of drugs due their structure which grants
them a range of advantages such as: enhances stability, increased rates of solubility and minimal
immunogenic properties (Gothwal et al., 2015). Encapsulation of nitric oxide - a compound with
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19RESEARCH PROPOSAL
vasodilatory properties, ability to regulate the proliferation of vascular cells and maintain
homoeostasis - is considered as a potential drug for cardio-protection, via encapsulation within
dendrimers. The characteristic structure of dendrimers comprising of a core and multiple
branches, allow for encapsulation and attachment of a wide range of substances with medicinal
and functional properties on the periphery of dendrimer branches hence allowing for attachments
and interactions with additional dendrimers present in the surrounding tissues (Gupta et al.,
2019). Further, the branched structure grants dendrimers the property of improve flexibility,
resulting in greater scope for multiple drug encapsulation and accessibility to wide range of
tissues with reduced possibility of premature drug leakage. A key disadvantage of dedrimers
however, is their large number of branches resulting in high charges which are excessively
anionic or cationic and hence may contribute to toxicity in the body (Chandarana, Curtis &
Hoskins, 2018).
Additionally, nanotechnology based encapsulation of berberine has been evidenced to
yield beneficial effects on cardiovascular profiles, in a number of studies. In the research
conducted by Guo et al., (2019), micelles of encapsulated berberine and a core of hydrophobic
alpha-tocopherol, along with a shell of polyethylene glycol-thiol, which was detachable was
formulated. An analysis of biodistribution demonstrated that berberine content in hepatic cells in
vivo was enhanced by 248.8%. The developed micelles also assisted in improvement of
metabolic profiles and reduction of plaque formation in the aorta in mice fed with a high fat diet.
Mice who were fed with a normal chow diet the levels of hepatic triglyceride, plasma
triglyceride, LDL cholesterol and total cholesterol were 3.32 ± 0.63 mg g−1, 0.54 ± 0.11 mmol
L−1, 0.40 ± 0.10 mmol L−1 and 3.43 ± 0.28 mmol L−1, respectively ( n = 10). Administration of a
high fat diet resulted in an increase of these levels (p < 0.001). Treatment with berberine
vasodilatory properties, ability to regulate the proliferation of vascular cells and maintain
homoeostasis - is considered as a potential drug for cardio-protection, via encapsulation within
dendrimers. The characteristic structure of dendrimers comprising of a core and multiple
branches, allow for encapsulation and attachment of a wide range of substances with medicinal
and functional properties on the periphery of dendrimer branches hence allowing for attachments
and interactions with additional dendrimers present in the surrounding tissues (Gupta et al.,
2019). Further, the branched structure grants dendrimers the property of improve flexibility,
resulting in greater scope for multiple drug encapsulation and accessibility to wide range of
tissues with reduced possibility of premature drug leakage. A key disadvantage of dedrimers
however, is their large number of branches resulting in high charges which are excessively
anionic or cationic and hence may contribute to toxicity in the body (Chandarana, Curtis &
Hoskins, 2018).
Additionally, nanotechnology based encapsulation of berberine has been evidenced to
yield beneficial effects on cardiovascular profiles, in a number of studies. In the research
conducted by Guo et al., (2019), micelles of encapsulated berberine and a core of hydrophobic
alpha-tocopherol, along with a shell of polyethylene glycol-thiol, which was detachable was
formulated. An analysis of biodistribution demonstrated that berberine content in hepatic cells in
vivo was enhanced by 248.8%. The developed micelles also assisted in improvement of
metabolic profiles and reduction of plaque formation in the aorta in mice fed with a high fat diet.
Mice who were fed with a normal chow diet the levels of hepatic triglyceride, plasma
triglyceride, LDL cholesterol and total cholesterol were 3.32 ± 0.63 mg g−1, 0.54 ± 0.11 mmol
L−1, 0.40 ± 0.10 mmol L−1 and 3.43 ± 0.28 mmol L−1, respectively ( n = 10). Administration of a
high fat diet resulted in an increase of these levels (p < 0.001). Treatment with berberine
20RESEARCH PROPOSAL
encapsulated micelles reduced these levels in mice as compared to the control of mice receiving
high fat diet with micelles (p > 0.05).
Research Limitations
Hence, as observed from the above, while extensive research remains on the emerging
potential and discovery of novel drug delivery systems using nanotechnology, there remains
limited evidence on current medical opinion on the use of such nanomedicines for the treatment
of CVDs. There also remains limited evidenced on the presence of any international guidelines
or recommended standards of usage on the correct dosage of nanomedicines to be administered
to prevent adverse consequences such as toxicity or environmental damage.
Research Value
The value of the following research lie in its ability to provide insights on current levels
of awareness and opinion on the efficacies of nanotechnology for the treatment of cardiovascular
diseases. Hence, gaining information on the current levels of knowledge on this innovative
intervention will further pave the way for incorporation of additional research such as
development of healthcare educational and promotional resources along with personnel training
frameworks on the usage of nanotechnology in disease treatment (Chauvierre & Letourneur,
2015). The development and implementation of such materials will assist in knowledge and skill
enhancement among staff and health professionals in healthcare organizations resulting in
nanotechnology and nanomedicine practice at optimum standards of quality and safety.
Information on present development of nanomedicines and their impact on patient health
outcomes, as will be provided by this research, will further prompt future studies on toxicity and
the need for international organization to formulate quality and safety standards essential for
encapsulated micelles reduced these levels in mice as compared to the control of mice receiving
high fat diet with micelles (p > 0.05).
Research Limitations
Hence, as observed from the above, while extensive research remains on the emerging
potential and discovery of novel drug delivery systems using nanotechnology, there remains
limited evidence on current medical opinion on the use of such nanomedicines for the treatment
of CVDs. There also remains limited evidenced on the presence of any international guidelines
or recommended standards of usage on the correct dosage of nanomedicines to be administered
to prevent adverse consequences such as toxicity or environmental damage.
Research Value
The value of the following research lie in its ability to provide insights on current levels
of awareness and opinion on the efficacies of nanotechnology for the treatment of cardiovascular
diseases. Hence, gaining information on the current levels of knowledge on this innovative
intervention will further pave the way for incorporation of additional research such as
development of healthcare educational and promotional resources along with personnel training
frameworks on the usage of nanotechnology in disease treatment (Chauvierre & Letourneur,
2015). The development and implementation of such materials will assist in knowledge and skill
enhancement among staff and health professionals in healthcare organizations resulting in
nanotechnology and nanomedicine practice at optimum standards of quality and safety.
Information on present development of nanomedicines and their impact on patient health
outcomes, as will be provided by this research, will further prompt future studies on toxicity and
the need for international organization to formulate quality and safety standards essential for
21RESEARCH PROPOSAL
preventing errors or adverse consequences to patients receiving undergoing nanotechnology
based disease treatments (Gardner, 2015).
Further, this research will also provide information on the impact of nanotechnology on
health outcomes of the patient, such as rates of mortality and quality of life, which will further
enhance the scope for future research on impact of nanotechnology on additional health
outcomes such as blood parameters or diagnostic results. Hence, the overall value of this
research lies in its ability to provide insights on current trends in healthcare technology and will
pave the way for future innovation in cardiovascular treatment and improved health outcomes in
patients (Oklu, Khademhosseini & Weiss, 2015).
Methodology
Research Design
A quantitative, retrospective, cross sectional research design will be used, which will
firstly involve a survey exploring the views, opinions and standards followed by health
professionals, preferably cardiologists and heart surgeons on the usage of nanotechnology for
treatment and improving the quality of life in patients with cardiovascular ailments. Additional
data on the mortality rate and quality of life of cardiovascular disease patients, across the age
groups of below 40 as well as above 40 years of age, receiving nanotechnology in comparison to
open-heart surgery will be collected. A quantitative research design is of relevance for this study
due to its incorporation numerical data in the form of mortality rates and quality of life scores
(Heale & Twycross, 2015). A cross sectional study has been considered in the research design
since it aims to explore data on health professionals’ view on nanotechnology in a particular
point of time (Watson, 2015).
preventing errors or adverse consequences to patients receiving undergoing nanotechnology
based disease treatments (Gardner, 2015).
Further, this research will also provide information on the impact of nanotechnology on
health outcomes of the patient, such as rates of mortality and quality of life, which will further
enhance the scope for future research on impact of nanotechnology on additional health
outcomes such as blood parameters or diagnostic results. Hence, the overall value of this
research lies in its ability to provide insights on current trends in healthcare technology and will
pave the way for future innovation in cardiovascular treatment and improved health outcomes in
patients (Oklu, Khademhosseini & Weiss, 2015).
Methodology
Research Design
A quantitative, retrospective, cross sectional research design will be used, which will
firstly involve a survey exploring the views, opinions and standards followed by health
professionals, preferably cardiologists and heart surgeons on the usage of nanotechnology for
treatment and improving the quality of life in patients with cardiovascular ailments. Additional
data on the mortality rate and quality of life of cardiovascular disease patients, across the age
groups of below 40 as well as above 40 years of age, receiving nanotechnology in comparison to
open-heart surgery will be collected. A quantitative research design is of relevance for this study
due to its incorporation numerical data in the form of mortality rates and quality of life scores
(Heale & Twycross, 2015). A cross sectional study has been considered in the research design
since it aims to explore data on health professionals’ view on nanotechnology in a particular
point of time (Watson, 2015).
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22RESEARCH PROPOSAL
Data Collection
For obtaining information on the responses of the chosen health professionals, a survey
will be conducted whose questions will be centered around to explore their understanding on
origins and principles of nanotechnology, the development of nanomedicines or nanoparticles
with therapeutic benefits, the role or the awareness of current research on the usage of such
substances in cardiac treatment and their impact on patient outcomes in comparison to common
interventions like oral medications and invasive surgeries. To explore the impact of
nanotechnology on health outcomes in cardiovascular patients, the mortality rates and quality of
life of cardiovascular patients across the age groups of below 40 as well as above 40 years of
age, receiving nanotechnology in comparison to open-heart surgery will be collected, from
administrative and patient clinical data available in the chosen healthcare organization. Quality
of life will be assessed in patients using the Minnesota Living with Heart Failure Questionnaire
(MLHFQ) (Bilbao et al., 2016).
Data Analysis
The data so obtained will be tested against the proposed hypothesis: Nanotechnology is
an effective cardiovascular intervention in terms of improvement of patient’s health outcomes,
mortality of life and overall quality of life as compared to traditional interventions such as oral
medications or invasive heart surgeries. Spreadsheet software like Microsoft Excel will be used
to collate and tabulate the data followed by usage of student’s t-test and Analysis of Variance
(ANNOVA) analytical methods to explore the presence of any statistically significant
differences in the mortality rates and quality of life scores between patients receiving
nanotechnology based nanomedicines and traditional interventions like medications and
surgeries (Aberson, 2019).
Data Collection
For obtaining information on the responses of the chosen health professionals, a survey
will be conducted whose questions will be centered around to explore their understanding on
origins and principles of nanotechnology, the development of nanomedicines or nanoparticles
with therapeutic benefits, the role or the awareness of current research on the usage of such
substances in cardiac treatment and their impact on patient outcomes in comparison to common
interventions like oral medications and invasive surgeries. To explore the impact of
nanotechnology on health outcomes in cardiovascular patients, the mortality rates and quality of
life of cardiovascular patients across the age groups of below 40 as well as above 40 years of
age, receiving nanotechnology in comparison to open-heart surgery will be collected, from
administrative and patient clinical data available in the chosen healthcare organization. Quality
of life will be assessed in patients using the Minnesota Living with Heart Failure Questionnaire
(MLHFQ) (Bilbao et al., 2016).
Data Analysis
The data so obtained will be tested against the proposed hypothesis: Nanotechnology is
an effective cardiovascular intervention in terms of improvement of patient’s health outcomes,
mortality of life and overall quality of life as compared to traditional interventions such as oral
medications or invasive heart surgeries. Spreadsheet software like Microsoft Excel will be used
to collate and tabulate the data followed by usage of student’s t-test and Analysis of Variance
(ANNOVA) analytical methods to explore the presence of any statistically significant
differences in the mortality rates and quality of life scores between patients receiving
nanotechnology based nanomedicines and traditional interventions like medications and
surgeries (Aberson, 2019).
23RESEARCH PROPOSAL
Data Variables
The hypothesis and statistical analysis of data obtained will be revolved around the
impact of nanotechnology as well as pharmaceuticals and surgeries on the variables of health
outcomes in patients. Hence, the mortality rate and quality life of patients will be the dependent
variables while the independent variables will comprise of cardiovascular interventions like
nanotechnology, oral medications and invasive surgery.
Sample Size and Recruitment
For the proposed research, random, purpose sampling methods will be conducted. This
will comprise of randomly recruiting health professionals, preferably cardiologists and cardiac
surgeons for the survey. Similarly, for the collection of data concerning mortality rates and
quality of life, patients who are suffering from cardiovascular diseases, preferably who have
encountered at least one episode of myocardial infarction or stroke, will be randomly recruited.
The sample of patients will be further divided into two groups, those who have received invasive
surgeries and pharmacological interventions and those who have received nanotechnology based
treatments. Both groups will further be divided into two sub groups: namely, patients below the
age of 40 years and patients above the age of 40 years. Random purposive sampling is the ideal
method for sample recruitment in this proposal since, a specific category of patients and health
professionals will be randomly recruited based on the research objectives (Etikan, Musa &
Alkassim, 2016). The sample size will be collected using the z-value, that is, using the following
formula: n = (Zσ/E)2, where ‘Z’ reflects the confidence level (for example: Z is equal to 1.96 got
95% confidence inrerval) to be used from the standard normal distribution, σ is the standard
deviation of the outcome variable and ‘E’. is the margin of error desired. This formula will
Data Variables
The hypothesis and statistical analysis of data obtained will be revolved around the
impact of nanotechnology as well as pharmaceuticals and surgeries on the variables of health
outcomes in patients. Hence, the mortality rate and quality life of patients will be the dependent
variables while the independent variables will comprise of cardiovascular interventions like
nanotechnology, oral medications and invasive surgery.
Sample Size and Recruitment
For the proposed research, random, purpose sampling methods will be conducted. This
will comprise of randomly recruiting health professionals, preferably cardiologists and cardiac
surgeons for the survey. Similarly, for the collection of data concerning mortality rates and
quality of life, patients who are suffering from cardiovascular diseases, preferably who have
encountered at least one episode of myocardial infarction or stroke, will be randomly recruited.
The sample of patients will be further divided into two groups, those who have received invasive
surgeries and pharmacological interventions and those who have received nanotechnology based
treatments. Both groups will further be divided into two sub groups: namely, patients below the
age of 40 years and patients above the age of 40 years. Random purposive sampling is the ideal
method for sample recruitment in this proposal since, a specific category of patients and health
professionals will be randomly recruited based on the research objectives (Etikan, Musa &
Alkassim, 2016). The sample size will be collected using the z-value, that is, using the following
formula: n = (Zσ/E)2, where ‘Z’ reflects the confidence level (for example: Z is equal to 1.96 got
95% confidence inrerval) to be used from the standard normal distribution, σ is the standard
deviation of the outcome variable and ‘E’. is the margin of error desired. This formula will
24RESEARCH PROPOSAL
provide the minimum amount of participants needed to make sure that E is not exceeded by the
margin of error in the confidence interval for the mean of the sample (Sullivan, 2019).
Ethical Considerations
To ensure that the proposed research is implemented without violating the personal and
professional interests of any individual or organization, ethical considerations will be adhered to
diligently (Dove et al., 2016). Prior to collecting data on patient profiles and views of health
professionals, written permission or consent will be obtained from the concerned health
organization. Further, health professionals and patients will be asked to voluntarily participate in
the research without any form of coercion. Patients must be assured that their decision to not
participate will not result in any hindrance to the quality of their treatment. Further for patients
and health professionals who are willing to participate, they will be assured that their identities
will be kept confidential along with explaining them the purpose of this research (Crawford et
al., 2019).
Surveys which are the key data collection method to be used in this research, are often
subject to biased responses from participants. Hence, the researcher will aim to use gentle
persuasion and provision of monetary rewards for participants if needed to prevent such bias.
Further, to ensure validity, the survey questionnaire will be peer-reviewed by more than one
researcher (Heale & Twycross, 2015). Lastly, for acknowledging the work of researchers whose
studies will be used for this research, the content will be paraphrased along with adequately
referencing and citing with author details (Walliman, 2017).
provide the minimum amount of participants needed to make sure that E is not exceeded by the
margin of error in the confidence interval for the mean of the sample (Sullivan, 2019).
Ethical Considerations
To ensure that the proposed research is implemented without violating the personal and
professional interests of any individual or organization, ethical considerations will be adhered to
diligently (Dove et al., 2016). Prior to collecting data on patient profiles and views of health
professionals, written permission or consent will be obtained from the concerned health
organization. Further, health professionals and patients will be asked to voluntarily participate in
the research without any form of coercion. Patients must be assured that their decision to not
participate will not result in any hindrance to the quality of their treatment. Further for patients
and health professionals who are willing to participate, they will be assured that their identities
will be kept confidential along with explaining them the purpose of this research (Crawford et
al., 2019).
Surveys which are the key data collection method to be used in this research, are often
subject to biased responses from participants. Hence, the researcher will aim to use gentle
persuasion and provision of monetary rewards for participants if needed to prevent such bias.
Further, to ensure validity, the survey questionnaire will be peer-reviewed by more than one
researcher (Heale & Twycross, 2015). Lastly, for acknowledging the work of researchers whose
studies will be used for this research, the content will be paraphrased along with adequately
referencing and citing with author details (Walliman, 2017).
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25RESEARCH PROPOSAL
Conclusion
This research proposal provides key insights on the role of nanotechnology in the
treatment of diseases like cardiovascular disorders., The rates of prevalence of cardiovascular
diseases and engagement of individuals in behavioral risk factors like consumption of high fat
and high sugar based diets, lack of physical activity and high adherence to smoking and alcohol
consumption are on the rise and hence, are key contributors to the global burden of
cardiovascular disease. In addition to modifying such unhealthy behaviors, oral medications and
invasive heart surgeries are the next common treatments for management of cardiovascular
diseases. Considering the adverse consequences of medication administration and surgeries,
coupled with the difficult to incorporate lifestyle changes, there is hence a need to incorporate
more robust forms of cardiac interventions which will also be free from complications.
Nanotechnology in this regard, prove to be an effective and innovative alternative.
Nanotechnology comprises of formulation and manipulation of equipment and products
at the nano scale level. Such substances or nanomedicines, have also been implicated to yield
therapeutic effects for the treatment of diseases, such as liposomes, micelles and dendrimers. At
present, a number of such substances are being developed with the aim of delivering
thrombolytic and cardio-protective drugs to the affected vascular tissues hence paving the way
for novel cardiovascular disease treatments. However, there lies limited evidence on the
knowledge, awareness and opinions of health professionals on the role of nanotechnology in
alleviating cardiovascular disease symptoms as well as their impact on improving health
outcomes in patients suffering from such conditions.
Hence, the following research proposal will aim to explore the opinions of health
professionals on the emerging importance of nanotechnology in cardiovascular disease treatment
Conclusion
This research proposal provides key insights on the role of nanotechnology in the
treatment of diseases like cardiovascular disorders., The rates of prevalence of cardiovascular
diseases and engagement of individuals in behavioral risk factors like consumption of high fat
and high sugar based diets, lack of physical activity and high adherence to smoking and alcohol
consumption are on the rise and hence, are key contributors to the global burden of
cardiovascular disease. In addition to modifying such unhealthy behaviors, oral medications and
invasive heart surgeries are the next common treatments for management of cardiovascular
diseases. Considering the adverse consequences of medication administration and surgeries,
coupled with the difficult to incorporate lifestyle changes, there is hence a need to incorporate
more robust forms of cardiac interventions which will also be free from complications.
Nanotechnology in this regard, prove to be an effective and innovative alternative.
Nanotechnology comprises of formulation and manipulation of equipment and products
at the nano scale level. Such substances or nanomedicines, have also been implicated to yield
therapeutic effects for the treatment of diseases, such as liposomes, micelles and dendrimers. At
present, a number of such substances are being developed with the aim of delivering
thrombolytic and cardio-protective drugs to the affected vascular tissues hence paving the way
for novel cardiovascular disease treatments. However, there lies limited evidence on the
knowledge, awareness and opinions of health professionals on the role of nanotechnology in
alleviating cardiovascular disease symptoms as well as their impact on improving health
outcomes in patients suffering from such conditions.
Hence, the following research proposal will aim to explore the opinions of health
professionals on the emerging importance of nanotechnology in cardiovascular disease treatment
26RESEARCH PROPOSAL
using survey questionnaires. Further, to explore the impact of nanotechnology on the health
outcomes of patients, data on mortality rates and quality of life scores will be collected and
compared between patients, below as well as above the age of 40 years, between receiving
nanotechnology and traditional interventions like oral medications and invasive surgeries. Using
statistical methods, the data will be tested against the proposed hypothesis.
This research will hence pave the way for obtaining insights on present clinical opinions
on the scope of nanotechnology in disease treatment and hence will provide scope to conduct
further research on providing education and training on this field. Further, obtaining data on
impact of nanotechnology on patient health outcomes will also enhance scope of future research
regarding levels of toxicity and effect on additional patient health parameters. To conclude,
nanaotechnology has also been subjected to doubts on levels of safety and hence there is need for
establishment of international standards on its usage in the future.
using survey questionnaires. Further, to explore the impact of nanotechnology on the health
outcomes of patients, data on mortality rates and quality of life scores will be collected and
compared between patients, below as well as above the age of 40 years, between receiving
nanotechnology and traditional interventions like oral medications and invasive surgeries. Using
statistical methods, the data will be tested against the proposed hypothesis.
This research will hence pave the way for obtaining insights on present clinical opinions
on the scope of nanotechnology in disease treatment and hence will provide scope to conduct
further research on providing education and training on this field. Further, obtaining data on
impact of nanotechnology on patient health outcomes will also enhance scope of future research
regarding levels of toxicity and effect on additional patient health parameters. To conclude,
nanaotechnology has also been subjected to doubts on levels of safety and hence there is need for
establishment of international standards on its usage in the future.
27RESEARCH PROPOSAL
References
Aberson, C. L. (2019). Applied power analysis for the behavioral sciences. Routledge.
Allijn, I. E., Czarny, B. M., Wang, X., Chong, S. Y., Weiler, M., Da Silva, A. E., ... & Storm, G.
(2017). Liposome encapsulated berberine treatment attenuates cardiac dysfunction after
myocardial infarction. Journal of controlled release, 247, 127-133.
Anderson, J. L., & Morrow, D. A. (2017). Acute myocardial infarction. New England Journal of
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Balakumar, P., Maung-U, K., & Jagadeesh, G. (2016). Prevalence and prevention of
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& Devereaux, P. J. (2015). Association between pre-operative statin use and major
cardiovascular complications among patients undergoing non-cardiac surgery: the
VISION study. European heart journal, 37(2), 177-185.
Bilbao, A., Escobar, A., García-Perez, L., Navarro, G., & Quirós, R. (2016). The Minnesota
living with heart failure questionnaire: comparison of different factor structures. Health
and quality of life outcomes, 14(1), 23.
Chandarana, M., Curtis, A., & Hoskins, C. (2018). The use of nanotechnology in cardiovascular
disease. Applied Nanoscience, 8(7), 1607-1619.
Chauvierre, C., & Letourneur, D. (2015). The European project NanoAthero to fight
cardiovascular diseases using nanotechnologies. Nanomedicine, 10(22), 3391-3400.
References
Aberson, C. L. (2019). Applied power analysis for the behavioral sciences. Routledge.
Allijn, I. E., Czarny, B. M., Wang, X., Chong, S. Y., Weiler, M., Da Silva, A. E., ... & Storm, G.
(2017). Liposome encapsulated berberine treatment attenuates cardiac dysfunction after
myocardial infarction. Journal of controlled release, 247, 127-133.
Anderson, J. L., & Morrow, D. A. (2017). Acute myocardial infarction. New England Journal of
Medicine, 376(21), 2053-2064.
Balakumar, P., Maung-U, K., & Jagadeesh, G. (2016). Prevalence and prevention of
cardiovascular disease and diabetes mellitus. Pharmacological research, 113, 600-609.
Berwanger, O., Le Manach, Y., Suzumura, E. A., Biccard, B., Srinathan, S. K., Szczeklik, W., ...
& Devereaux, P. J. (2015). Association between pre-operative statin use and major
cardiovascular complications among patients undergoing non-cardiac surgery: the
VISION study. European heart journal, 37(2), 177-185.
Bilbao, A., Escobar, A., García-Perez, L., Navarro, G., & Quirós, R. (2016). The Minnesota
living with heart failure questionnaire: comparison of different factor structures. Health
and quality of life outcomes, 14(1), 23.
Chandarana, M., Curtis, A., & Hoskins, C. (2018). The use of nanotechnology in cardiovascular
disease. Applied Nanoscience, 8(7), 1607-1619.
Chauvierre, C., & Letourneur, D. (2015). The European project NanoAthero to fight
cardiovascular diseases using nanotechnologies. Nanomedicine, 10(22), 3391-3400.
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28RESEARCH PROPOSAL
Columbo, J. A., Lambour, A. J., Sundling, R. A., Chauhan, N. B., Bessen, S. Y., Linshaw, D.
L., ... & Stone, D. H. (2018). A meta-analysis of the impact of aspirin, clopidogrel, and
dual antiplatelet therapy on bleeding complications in noncardiac surgery. Annals of
surgery, 267(1), 1-10.
Cooke, J. P., & Atkins, J. (2016). Nanotherapeutic solutions for cardiovascular
disease. Methodist DeBakey cardiovascular journal, 12(3), 132.
Cooke, J. P., & Atkins, J. (2016). Nanotherapeutic solutions for cardiovascular disease.
Methodist DeBakey cardiovascular journal, 12(3), 132.
Crawford, S., Hokke, S., Nicholson, J. M., Zion, L., Lucke, J., Keyzer, P., & Hackworth, N.
(2019). “It’s not black and white” Public health researchers’ and ethics committees’
perceptions of engaging research participants online. Internet Research, 29(1), 123-143.
Dadjou, Y., Safavi, S., &Kojuri, J. (2016). Risks and Benefits of Dual Antiplatelet Therapy
Beyond 12 Months After Coronary Stenting: A Prospective Randomized Cohort Study.
Medicine, 95(22).
Dove, E. S., Townend, D., Meslin, E. M., Bobrow, M., Littler, K., Nicol, D., ... & Shabani, M.
(2016). Ethics review for international data-intensive research. Science, 351(6280), 1399-
1400.
Elmariah, S., Doros, G., Benavente, O. R., Bhatt, D. L., Connolly, S. J., Yusuf, S., ...& Mauri, L.
(2018). Impact of clopidogrel therapy on mortality and cancer in patients with
cardiovascular and cerebrovascular disease: a patient-level meta-analysis. Circulation:
Cardiovascular Interventions, 11(1), e005795.
Columbo, J. A., Lambour, A. J., Sundling, R. A., Chauhan, N. B., Bessen, S. Y., Linshaw, D.
L., ... & Stone, D. H. (2018). A meta-analysis of the impact of aspirin, clopidogrel, and
dual antiplatelet therapy on bleeding complications in noncardiac surgery. Annals of
surgery, 267(1), 1-10.
Cooke, J. P., & Atkins, J. (2016). Nanotherapeutic solutions for cardiovascular
disease. Methodist DeBakey cardiovascular journal, 12(3), 132.
Cooke, J. P., & Atkins, J. (2016). Nanotherapeutic solutions for cardiovascular disease.
Methodist DeBakey cardiovascular journal, 12(3), 132.
Crawford, S., Hokke, S., Nicholson, J. M., Zion, L., Lucke, J., Keyzer, P., & Hackworth, N.
(2019). “It’s not black and white” Public health researchers’ and ethics committees’
perceptions of engaging research participants online. Internet Research, 29(1), 123-143.
Dadjou, Y., Safavi, S., &Kojuri, J. (2016). Risks and Benefits of Dual Antiplatelet Therapy
Beyond 12 Months After Coronary Stenting: A Prospective Randomized Cohort Study.
Medicine, 95(22).
Dove, E. S., Townend, D., Meslin, E. M., Bobrow, M., Littler, K., Nicol, D., ... & Shabani, M.
(2016). Ethics review for international data-intensive research. Science, 351(6280), 1399-
1400.
Elmariah, S., Doros, G., Benavente, O. R., Bhatt, D. L., Connolly, S. J., Yusuf, S., ...& Mauri, L.
(2018). Impact of clopidogrel therapy on mortality and cancer in patients with
cardiovascular and cerebrovascular disease: a patient-level meta-analysis. Circulation:
Cardiovascular Interventions, 11(1), e005795.
29RESEARCH PROPOSAL
Etikan, I., Musa, S. A., & Alkassim, R. S. (2016). Comparison of convenience sampling and
purposive sampling. American journal of theoretical and applied statistics, 5(1), 1-4.
Gardner, J. (2015). Nanotechnology in medicine and healthcare: possibilities, progress and
problems: education and training. South African Journal of Bioethics and Law, 8(2), 50-
53.
Gothwal, A., Kesharwani, P., Gupta, U., Khan, I., Cairul Iqbal Mohd Amin, M., Banerjee, S., &
K Iyer, A. (2015). Dendrimers as an effective nanocarrier in cardiovascular
disease. Current pharmaceutical design, 21(30), 4519-4526.
Guo, H. H., Feng, C. L., Zhang, W. X., Luo, Z. G., Zhang, H. J., Zhang, T. T., ... & Abliz, Z.
(2019). Liver-target nanotechnology facilitates berberine to ameliorate cardio-metabolic
diseases. Nature communications, 10(1), 1981.
Gupta, P., Garcia, E., Sarkar, A., Kapoor, S., Rafiq, K., Chand, H. S., & Jayant, R. D. (2019).
Nanoparticle based treatment for cardiovascular diseases. Cardiovascular &
Haematological Disorders-Drug Targets (Formerly Current Drug Targets-
Cardiovascular & Hematological Disorders), 19(1), 33-44.
Hassan, K., Bayer, N., Schlingloff, F., Oberhoffer, M., Wohlmuth, P., Schmoeckel, M., &Geidel,
S. (2018). Bleeding complications after use of novel oral anticoagulants in patients
undergoing cardiac surgery. The Annals of thoracic surgery, 105(3), 702-708.
Heale, R., & Twycross, A. (2015). Validity and reliability in quantitative studies. Evidence-
based nursing, 18(3), 66-67.
Etikan, I., Musa, S. A., & Alkassim, R. S. (2016). Comparison of convenience sampling and
purposive sampling. American journal of theoretical and applied statistics, 5(1), 1-4.
Gardner, J. (2015). Nanotechnology in medicine and healthcare: possibilities, progress and
problems: education and training. South African Journal of Bioethics and Law, 8(2), 50-
53.
Gothwal, A., Kesharwani, P., Gupta, U., Khan, I., Cairul Iqbal Mohd Amin, M., Banerjee, S., &
K Iyer, A. (2015). Dendrimers as an effective nanocarrier in cardiovascular
disease. Current pharmaceutical design, 21(30), 4519-4526.
Guo, H. H., Feng, C. L., Zhang, W. X., Luo, Z. G., Zhang, H. J., Zhang, T. T., ... & Abliz, Z.
(2019). Liver-target nanotechnology facilitates berberine to ameliorate cardio-metabolic
diseases. Nature communications, 10(1), 1981.
Gupta, P., Garcia, E., Sarkar, A., Kapoor, S., Rafiq, K., Chand, H. S., & Jayant, R. D. (2019).
Nanoparticle based treatment for cardiovascular diseases. Cardiovascular &
Haematological Disorders-Drug Targets (Formerly Current Drug Targets-
Cardiovascular & Hematological Disorders), 19(1), 33-44.
Hassan, K., Bayer, N., Schlingloff, F., Oberhoffer, M., Wohlmuth, P., Schmoeckel, M., &Geidel,
S. (2018). Bleeding complications after use of novel oral anticoagulants in patients
undergoing cardiac surgery. The Annals of thoracic surgery, 105(3), 702-708.
Heale, R., & Twycross, A. (2015). Validity and reliability in quantitative studies. Evidence-
based nursing, 18(3), 66-67.
30RESEARCH PROPOSAL
Heusch, G., &Gersh, B. J. (2016). The pathophysiology of acute myocardial infarction and
strategies of protection beyond reperfusion: a continual challenge. European heart
journal, 38(11), 774-784.
Hulsegge, G., Looman, M., Smit, H. A., Daviglus, M. L., van der Schouw, Y. T., &Verschuren,
W. M. (2016). Lifestyle changes in young adulthood and middle age and risk of
cardiovascular disease and all‐cause mortality: The Doetinchem Cohort Study. Journal of
the American Heart Association, 5(1), e002432.
Ibanez, B., Heusch, G., Ovize, M., & Van de Werf, F. (2015). Evolving therapies for myocardial
ischemia/reperfusion injury. Journal of the American College of Cardiology, 65(14),
1454-1471.
Jafri, S. K., Ehsan, L., Abbas, Q., Ali, F., Chand, P., & Haque, A. U. (2017). Frequency and
outcome of acute neurologic complications after congenital heart disease
surgery. Journal of pediatric neurosciences, 12(4), 328.
Jain, K., Kumar Mehra, N., & K Jain, N. (2015). Nanotechnology in drug delivery: safety and
toxicity issues. Current pharmaceutical design, 21(29), 4252-4261.
Jurj, A., Braicu, C., Pop, L. A., Tomuleasa, C., Gherman, C. D., &Berindan-Neagoe, I. (2017).
The new era of nanotechnology, an alternative to change cancer treatment. Drug design,
development and therapy, 11, 2871.
Karimi, M., Zare, H., Bakhshian Nik, A., Yazdani, N., Hamrang, M., Mohamed, E., ... &
Hamblin, M. R. (2016). Nanotechnology in diagnosis and treatment of coronary artery
disease. Nanomedicine, 11(5), 513-530.
Heusch, G., &Gersh, B. J. (2016). The pathophysiology of acute myocardial infarction and
strategies of protection beyond reperfusion: a continual challenge. European heart
journal, 38(11), 774-784.
Hulsegge, G., Looman, M., Smit, H. A., Daviglus, M. L., van der Schouw, Y. T., &Verschuren,
W. M. (2016). Lifestyle changes in young adulthood and middle age and risk of
cardiovascular disease and all‐cause mortality: The Doetinchem Cohort Study. Journal of
the American Heart Association, 5(1), e002432.
Ibanez, B., Heusch, G., Ovize, M., & Van de Werf, F. (2015). Evolving therapies for myocardial
ischemia/reperfusion injury. Journal of the American College of Cardiology, 65(14),
1454-1471.
Jafri, S. K., Ehsan, L., Abbas, Q., Ali, F., Chand, P., & Haque, A. U. (2017). Frequency and
outcome of acute neurologic complications after congenital heart disease
surgery. Journal of pediatric neurosciences, 12(4), 328.
Jain, K., Kumar Mehra, N., & K Jain, N. (2015). Nanotechnology in drug delivery: safety and
toxicity issues. Current pharmaceutical design, 21(29), 4252-4261.
Jurj, A., Braicu, C., Pop, L. A., Tomuleasa, C., Gherman, C. D., &Berindan-Neagoe, I. (2017).
The new era of nanotechnology, an alternative to change cancer treatment. Drug design,
development and therapy, 11, 2871.
Karimi, M., Zare, H., Bakhshian Nik, A., Yazdani, N., Hamrang, M., Mohamed, E., ... &
Hamblin, M. R. (2016). Nanotechnology in diagnosis and treatment of coronary artery
disease. Nanomedicine, 11(5), 513-530.
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31RESEARCH PROPOSAL
Kuzmov, A., &Minko, T. (2015). Nanotechnology approaches for inhalation treatment of lung
diseases. Journal of Controlled Release, 219, 500-518.
Lakshmanan, R., &Maulik, N. (2018). Development of next generation cardiovascular
therapeutics through bio‐assisted nanotechnology. Journal of Biomedical Materials
Research Part B: Applied Biomaterials, 106(5), 2072-2083.
Lesnefsky, E. J., Chen, Q., Tandler, B., &Hoppel, C. L. (2017). Mitochondrial dysfunction and
myocardial ischemia-reperfusion: implications for novel therapies. Annual review of
pharmacology and toxicology, 57, 535-565.
Luan, J., & Zhai, G. (2016). Targeted drug delivery for cardiovascular and cerebrovascular
diseases. Current drug targets, 17(4), 467-474.
Maher, K. O. (2018). Nanomedicine and nanotechnology for heart failure research, diagnosis,
and treatment. In Heart failure in the child and young adult (pp. 779-784). Academic
Press.
Matoba, T., Koga, J. I., Nakano, K., Egashira, K., & Tsutsui, H. (2017). Nanoparticle-mediated
drug delivery system for atherosclerotic cardiovascular disease. Journal of
cardiology, 70(3), 206-211.
Oklu, R., Khademhosseini, A., & Weiss, P. S. (2015). Patient-inspired engineering and
nanotechnology.
Prajnamitra, R. P., Chen, H. C., Lin, C. J., Chen, L. L., & Hsieh, P. C. H. (2019).
Nanotechnology Approaches in Tackling Cardiovascular Diseases. Molecules, 24(10),
2017.
Kuzmov, A., &Minko, T. (2015). Nanotechnology approaches for inhalation treatment of lung
diseases. Journal of Controlled Release, 219, 500-518.
Lakshmanan, R., &Maulik, N. (2018). Development of next generation cardiovascular
therapeutics through bio‐assisted nanotechnology. Journal of Biomedical Materials
Research Part B: Applied Biomaterials, 106(5), 2072-2083.
Lesnefsky, E. J., Chen, Q., Tandler, B., &Hoppel, C. L. (2017). Mitochondrial dysfunction and
myocardial ischemia-reperfusion: implications for novel therapies. Annual review of
pharmacology and toxicology, 57, 535-565.
Luan, J., & Zhai, G. (2016). Targeted drug delivery for cardiovascular and cerebrovascular
diseases. Current drug targets, 17(4), 467-474.
Maher, K. O. (2018). Nanomedicine and nanotechnology for heart failure research, diagnosis,
and treatment. In Heart failure in the child and young adult (pp. 779-784). Academic
Press.
Matoba, T., Koga, J. I., Nakano, K., Egashira, K., & Tsutsui, H. (2017). Nanoparticle-mediated
drug delivery system for atherosclerotic cardiovascular disease. Journal of
cardiology, 70(3), 206-211.
Oklu, R., Khademhosseini, A., & Weiss, P. S. (2015). Patient-inspired engineering and
nanotechnology.
Prajnamitra, R. P., Chen, H. C., Lin, C. J., Chen, L. L., & Hsieh, P. C. H. (2019).
Nanotechnology Approaches in Tackling Cardiovascular Diseases. Molecules, 24(10),
2017.
32RESEARCH PROPOSAL
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Nanotechnology Approaches in Tackling Cardiovascular Diseases. Molecules, 24(10),
2017.
Rahi, A., Sattarahmady, N., & Heli, H. (2015). Toxicity of nanomaterials-physicochemical
effects.
Savaliya, R., Shah, D., Singh, R., Kumar, A., Shanker, R., Dhawan, A., & Singh, S. (2015).
Nanotechnology in disease diagnostic techniques. Current drug metabolism, 16(8), 645-
661.
Scheitz, J. F., MacIsaac, R. L., Abdul-Rahim, A. H., Siegerink, B., Bath, P. M., Endres, M., ...&
Nolte, C. H. (2016). Statins and risk of poststrokehemorrhagic complications. Neurology,
86(17), 1590-1596.
Sharma, D., Sisodia, A., Devgarha, S., &Mathur, R. M. (2016). Evaluation of early postoperative
complications after open heart surgery in Hepatitis-B positive patients. Heart India, 4(2),
56.
Singh, H. (2016). Nanotechnology applications in functional foods; opportunities and challenges.
Preventive nutrition and food science, 21(1), 1.
Sullivan, L. (2019). Power and Sample Size Determination. Retrieved 1 August 2019, from
http://sphweb.bumc.bu.edu/otlt/MPH
Modules/BS/BS704_Power/BS704_Power_print.html.
33RESEARCH PROPOSAL
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treatment: From molecular level to nanotechnology. Current pharmaceutical
design, 21(30), 4367.
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angiogenesis therapeutics by redox injectable hydrogel-Regulation of local nitric oxide
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from https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds).
World Health Organization. (2019). Obesity and overweight. Retrieved 26 July 2019, from
https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
Vaidya, B., & Gupta, V. (2015). Novel therapeutic strategies for cardiovascular diseases
treatment: From molecular level to nanotechnology. Current pharmaceutical
design, 21(30), 4367.
Vong, L. B., Bui, T. Q., Tomita, T., Sakamoto, H., Hiramatsu, Y., & Nagasaki, Y. (2018). Novel
angiogenesis therapeutics by redox injectable hydrogel-Regulation of local nitric oxide
generation for effective cardiovascular therapy. Biomaterials, 167, 143-152.
Walliman, N. (2017). Research methods: The basics. Routledge.
Watson, R. (2015). Quantitative research. Nursing Standard (2014+), 29(31), 44.
Westman, P. C., Lipinski, M. J., Luger, D., Waksman, R., Bonow, R. O., Wu, E., & Epstein, S.
E. (2016). Inflammation as a driver of adverse left ventricular remodeling after acute
myocardial infarction. Journal of the American College of Cardiology, 67(17), 2050-
2060.
World Health Organization. (2019). Cardiovascular diseases (CVDs). Retrieved 26 July 2019,
from https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds).
World Health Organization. (2019). Obesity and overweight. Retrieved 26 July 2019, from
https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
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