PRODIGIOSIN ENCAPSULATED POLY LACTIDE-CO-GLYCOLIDE (PLGA)-COATED STENT FOR CORONARY CARDIOVASCULAR INTERVENTIONS

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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. As a result, over 80% of all deaths due to CVDs occur in

low and middle-income countries. This huge statistical disproportion in low and middle income.....


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