Prodigiosin Encapsulated Poly Lactide-Co-Glycolide (PLGA)- Coated Stent for Coronary Cardiovascular Interventions.
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.
TABLE OF CONTENTS
ABSTRACT.. ii
DEDICATION…… iii
Table of Contents.. v
List of Figures… viii
CHAPTER ONE BACKGROUND AND INTRODUCTION
- STATEMENT OF THE PROBLEM…………………. 2
- CORONARY ARTERY DISEASE (ATHEROSCLEROSIS)…….. 3
- Mechanism of Atherosclerosis…….. 4
- Treatment Trends……….. 9
- UNRESOLVED ISSUES……… 10
- SCOPE OF WORK……… 14
References……. 14
CHAPTER TWO LITERATURE REVIEW
- DRUG ELUTING STENTS (DESs)………. 17
- First Generation Drug Eluting Stents……… 18
- COATING OF STENTS……… 26
- Spraying of Stent……………. 28
- Ultrasonic Nozzles for Stent Coating….. 30
- Electronanospray…….. 32
- CONTROL DELIVERY OF DRUG…………… 34
- Drug Release Mechanisms………… 36
- Factors Influencing Drug Release…… 38
- Drug Delivery from stents… 38
- DRUG-POLYMER ADHESION……. 45
- Polymer-Stent Adhesion… 47
References….. 48
CHAPTER THREE METHODOLOGY
- MATERIALS AND METHOD….. 56
COATING OF STENTS…. 57
- PREPARATION OF PBS SOLUTION……. 58
- PURIFICATION OF PRODIGIOSIN………. 59
- COATING METHODS.. 59
References…. 60
CHAPTER FOUR DISCUSSION OF RESULTS
- PROSCOPE ANALYSIS… 61
- PHASES OF DRUG RELEASE………. 64
4.4 Gravimetric Analysis… 71
4.3 UV-VIS SPECTROPHOTOMETRY………… 72
References…………… 73
CHAPTER FIVE CONCLUSION AND FUTURE WORK
- CONCLUSION……. 75
- FUTURE WORK…. 76
NEW STENT COATING TECHNOLOGY 77
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].
REFERENCES
Abizaid A., and Ribamar C. J. Advances in Interventional Cardiology:New Drug-Eluting Stents, An Overview on Biodegradable and Polymer-Free Next-Generation Stent SystemsCirculation: Cardiovascular Interventions.2010; 3: 384-393
Berry C. Tardif J.C., Bourassa M.G., Coronary Heart Disease in Patients with Diabetes: part II: recent advances in coronary revascularization. J Am Coll Cardiol 2007; 49:643-56
Engineer C., Parikh J. and Raval A., Hydrolytic Degradation Behavior of 50/50 Poly Lactide-co-Glycolide from Drug Eluting Stents, Trends Biomater. Artif., 2010, 24(3):131-138.
Vey E., Roger C., Meehan L., Booth J., Claybourn M., Miller A.F. and Saiani A., “Degradation mechanism of poly(lactic-co-glycolic) acid block copolymer cast films in phosphate buffer solution”, Polym. Degrad. Stab. 93, 1869–1876 (2008)
Hurrell S. and Cameron R.E., “Polyglycolide: degradation and drug release. Part I. Changes in morphology during degradation”, J. Mater. Sci. Mater. Med. 12(9), 811–816 (2001).
Holmes D.R., Kereiakes, D.J., Garg, S., et al. Stent thrombosis. J Am Coll Cardiol 2010;56:1357-65.