Paclitaxel Loaded Polylactide-Co-Glycolide Acids For Coronary Artery : Current School News

Paclitaxel Loaded Polylactide-Co-Glycolide Acids For Coronary Artery Disease and Cancer Treatment

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Paclitaxel Loaded Polylactide-Co-Glycolide Acids For Coronary Artery Disease and Cancer Treatment.

ABSTRACT

The number one killer disease in the world is Cardiovascular Disease1. The most serious element of Cardiovascular Disease is Coronary Artery Disease.

Currently, the main treatment for Coronary Artery Disease is stent placement surgery. However, its long time safety and efficiency are the major setbacks, as it is associated with late restenosis and late thrombosis.

These are set caused by the durable polymeric film used as the drug carrier. To improve on the current treatment (stent placement surgery), a biodegradable drug delivery system was synthesized.

Paclitaxel was successfully entrapped into the polylactide-co-glycolide acids microspheres via single solvent microencapsulation evaporation method. Optical Microscopy was used to study the shape and morphology of the microspheres. The particle sizes were found to range of the microspheres is 15. 18 – 40.11 µm, with a mean size of 29.415 µm, a p-value 0.986 and a z-value-0.02.

The results suggest that the encapsulated drug loaded microspheres can be used as biodegradable drug eluting structures for localized vascular-targeted therapy for the treatment of coronary artery disease.

This is a presented as potential alternative to stent placement surgery. The potential extensions to localized cancer treatment are also elucidated.

TABLE OF CONTENTS

TITLE PAGE ERROR! BOOKMARK NOT DEFINED.
DEDICATION II
ABSTRACT III
ACKNOWLEDGEMENT IV
LIST OF FIGURES VII
LIST OF TABLES IX

CHAPTER ONE

1.0 BACKGROUND AND INTRODUCTION 1
1.1 STATEMENT OF THE PROBLEM (HEART DISEASE) 1
1.2 CORONARY ARTERY DISEASE 3
1.2.1 MECHANISM OF CORONARY ARTERY DISEASE (ATHEROSCLEROSIS) 3
1.2.2 PAST TREATMENT AND CURRENT TREATMENT ON CORONARY ARTERY DISEASE (ATHEROSCLEROSIS) 8
1.3 UNRESOLVED ISSUES 8
1.4 SCOPE OF WORK 9

CHAPTER TWO

2.0 LITERATURE REVIEW 11
2.1 STENTS AND DRUG ELUTING STENTS 11
2.2 DRUG ELUTING STENTS 13
2.2.0 FIRST GENERATION DRUG ELUTING STENTS 17
2.2.1 CYPHER-SIROLIMUS DRUG ELUTING STENTS (SES) 17
2.2.2 THE TAXUS-PACLITAXEL-DRUG ELUTING STENTS (PES) 18
2.3 THE SECOND GENERATION DRUG ELUTING STENTS 21
2.3.1 THE ENDEAVOR ZES 21
2.3.2 THE XIENCE-V EES 22
2.5 NEVOTM SIROLIMOUS CORONARY STENT 24
2.6 POLYLACTIDE –CO-GLYCOLIDE ACIDS (PLGA) 25
2.7 MICRO ENCAPSULATION OF THERAPEUTIC AGENT WITHIN THE PLGA
(SINGLE EMULTION PROCESS) 27

CHAPTER THREE

3.0 MATERIALS AND METHODS 36
3.1 MATERIALS FOR SINGLE EMULSION ENCAPSULATION AND WATER ABSORPTION 36
3.2 WATER ADSORPTION BY POLYLACTIDE-CO-GLYCOLIDE ACIDS (PLGAS) 37
3.2.1 EXPERIMENTAL METHODS 37
3.3 SINGLE EMULSION MICRO-ENCAPSULATION METHOD 38
3.3.1 ROLE OF POLY VINYL ALCOHOL STABILIZER 39
3.3.2 PREPARATION OF AQUEOUS PVA SOLUTION 40
3.3.3 DISSOLUTION OF POLYLACTIDE-CO-GLYCOLIDE ACID 41
EXPERIMENTAL PROCEDURE 42
3.3.4 HARDENING OF THE MICROSPHERES AND REMOVAL OF ORGANIC SOLVENT 44
3.4 EXPERIMENTS ON DRUG LOADING EFFICIENCY 46
3.4.1 PREPARATION OF PHOSPHATE BUFFER SALINE SOLUTION 47
3.4.2 UV ABSORBANCE FOR STANDARD SOLUTIONS OF PACLITAXEL 48

CHAPTER FOUR

4.0 RESULTS AND DISCUSSION 52
4.1 WATER ABSORPTION OF POLYLACTIDE-CO-GLYCOLIDE ACIDS 52
4.2 PARTICLE SIZE, SHAPE AND MORPHOLOGY 59
4.3 PARTICLE SIZE ANALYSIS 61
4.4 HYPOTHESIS TEST 66

CHAPTER FIVE

5.0 CONCLUSIONS AND RECOMMENDATIONS 72
5.1 CONCLUSIONS 72
5.2 RECOMMENDATIONS 72

INTRODUCTION

Statement of the Problem (Heart Disease)

Cardiovascular disease (CVD) is caused by disorders of the heart and blood vessels, which includes coronary heart disease (heart attacks), cerebrovascular disease (stroke), raised blood pressure (hypertension), peripheral artery disease, rheumatic heart disease, congenital heart disease and heart failure [1,2]. The first two are the major killer diseases in the whole world.

In 2002, it was estimated that 29% of deaths worldwide (16.7 million deaths) were due to CVD and that 43% of global morbidity and mortality, measured in disability-adjusted life years (DALYs), and was caused by CVD [1].

Furthermore, 78% of global mortality and 86% of mortality and morbidity from CVD occurs in developing countries.

In 2008, about 17.3 million people died as a result of cardiovascular disease. These represent 30% of the global death toll 2008. Out of  this figure, 7.3 million were due to coronary heart 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. 80% of cardiovascular disease, that is 5.8 million deaths, occurs in low and medium income countries.

Furthermore, Coronary Artery Disease (CAD) is the number one causes of death in both males and females in the low-income and high-income countries [3]. There is, therefore, a need for improved methods for the treatment of CAD in both developed and developing countries [3].

REFERNCES

Hirenkumar Makadia 1 and Steven J. Siegel : Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier, Polymers 2011, 3, 1377-1397; doi: 10.3390/polym3031377

Caiping Lin : Biodegradable Polymers in Drug Delivery, Chemical Department College of Environmental Science and Forestry State University of New York, 2005

Celestron Digital Microscope (Model #44345LCD Deluxe Digital Microscope) Manual

Babatunde Ogunnaike : Random Phenomena ,Fundamentals of Probability & Statistics for Engineers, Taylor & Francis, May 20, 2011, pg 548-633

Tiago Ferreira: Image J user guide IJ 1.46r , October, 2012

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