ABSTRACT
This research focuses on the design of a robust but flexible
prodigiosin eluting stent coating for possible coronary cardiovascular
implant. When coated with the drug embedded polymer matrix, the stent
would be expected to dilate the vessel around the fatty blockages while
the drug eluting polymer membrane delivers anti-proliferative drugs over
a period of time to prevent the restenosis that otherwise would occur.
The goal of this work is to incorporate anti-cancerous drug prodigiosin
in the PLGA polymer matrix and then ascertain its release kinetics. In
this research, Poly vinyl Pyrrolidone was used as a binder and
cross-linker to create adhesion between the metallic stent strut and the
drug encapsulated polymer matrix as well as between the polymer and the
drug. This work also explores diffusion and degradation phenomena to
explain the transport, dissemination, dispersion and absorption of drugs
at the interface between the stent and the vessel wall. The expected
results will then be discussed for potential applications via the
incorporation of these prodigiosin-eluting stents for the treatment of
coronary cardiovascular diseases.
CHAPTER ONE
1.0 BACKGROUND AND INTRODUCTION
Cardiovascular disease is currently the leading cause of death in
Africa and the world at large, accounting for at least 30% of all death.
One of the major causes of cardiovascular disease is arteriosclerosis.
It is as a consequence of the build-up of fatty cells and tissues within
blood vessels. In most cases, this built-up is not detected until
complete blockage which prevents the flow of blood and subsequently
leads to heart attack, stroke or death. The objective is to develop
prodigiosin embedded polymer-coated cardiovascular stents that will
successfully deliver drugs and bioactive agents to blood vessels and
treat coronary cardiovascular diseases while at the same time preventing
restenosis-the narrowing of the blood vessel after angioplastic
procedure. The polymer earmarked for these biodegradable coating is poly
lactic-co-glycolic acid (PLGA) because of it biocompatibility and high
rate of biodegradation. Over the past decade, drug eluting stents have
been used to treat arteriosclerosis. Essentially, the stent dilate the
vessel around the fatty blockages while the drug eluting coatings
deliver anti-cancer drugs to prevent the restenosis that otherwise would
occur. However, the stents remain permanently in the blood vessels
after the duration of drug elution. Furthermore, vessel irritation,
endothelial dysfunction, vessel hypersensitivity and chronic
inflammation at the site of implantation are critical parameters that
have attracted serious attention. There is therefore a need for
multi-component, multifunctional materials for novel cardiovascular
stents whereby, one important function should be degradability of the
polymer so that after degradation, a functional vessel wall is
regenerated [1].
There is also an equal need for reasonable stent coatings that can
degrade gradually and be absorbed slowly by the body without creating
the afore-mentioned adverse side effects.
1.1 STATEMENT OF THE PROBLEM
Cardiovascular disease (CVD) is a result of the disorder of the heart
and blood vessels. Atherosclerosis, the main cause of coronary artery
disease (CAD), is an inflammatory disease in which immune mechanisms
interact with metabolic risk factors to initiate, propagate and activate
lesions in the arterial wall [2]. About two decades ago, it was widely
expected that the treatment of hypercholesterolemia and hypertension
would eliminate CADs by the end of the 20th century but this has not
been the case. CVDs include coronary heart disease (heart attacks),
cerebrovascular disease (stroke), high blood pressure (hypertension),
peripheral artery disease, rheumatic heart disease, congenital heart
disease, and heart failures [3]. The first two are the foremost causes
of death in Africa and the world over. In 2008, about 17.3 million
deaths were as a result of cardiovascular diseases. These represented
30% of the global death toll in 2008. Out of this figure, 7.3 million
were due to coronary artery disease (Atherosclerosis), 6.2 million were
due to stroke and 5.8 million were jointly caused by hypertension, high
blood pressure, diabetes, and heart failure. Moreover, Coronary Artery
Disease (CAD) is the principal cause of death in both males and females
in the low-income and high-income countries. There is, therefore, an
urgent need for improved approaches for the treatment of CAD in both
developed developing and underdeveloped countries. People in low and
middle-income countries are usually more exposed to risk factors of CVDs
and do not often benefit from prevention programs as do people in
high-income countries