WWW.DISSERTATION.XLIBX.INFO
FREE ELECTRONIC LIBRARY - Dissertations, online materials
 
<< HOME
CONTACTS



Pages:   || 2 | 3 | 4 | 5 |   ...   | 8 |

«By Rucha Joshi Thesis Submitted to the Faculty of the Graduate School of Vanderbilt University in partial fulfillment of the requirements for the ...»

-- [ Page 1 ] --

Smart Microspheres for Stimuli Responsive Drug Delivery

By

Rucha Joshi

Thesis

Submitted to the Faculty of the

Graduate School of Vanderbilt University

in partial fulfillment of the requirements

for the degree of

MASTER OF SCIENCE

in

Biomedical Engineering

December, 2011

Nashville, Tennessee

Approved:

Dr. Craig L. Duvall

Dr. Hak-Joon Sung

To my amazing parents, Vinay and Deepa, and

To my global fellow brothers and sisters deprived of education i

ACKNOWLEDGEMENTS

First of all, I am very thankful to Prof. Dr. Craig Duvall, my thesis adviser for his extensive personal and professional guidance. As my thesis adviser and mentor, he has taught me more than I could ever give him credit for here. He has shown me, by his example, what a good scientist and person should be. Calm and understanding, he has always been there to discuss any aspect of research whenever I wanted. I am also obliged to Prof. Dr. Hak- Joon Sung, my co-adviser, for his valuable feedback and guidance on my research from time to time. I am also indebted to him for being supportive of my career goals and encouraging me to pursue them with enthusiasm.

I would also like to express my sincere thanks to my lab mates, especially Chris Nelson, Brian Evans, Spencer Crowder, Angela Zachman, Lucas Hofmeister, Shann Yu and Dr. Hongmei Li for teaching me different instrumental techniques. Special thanks to Dr. Mukesh Gupta in our laboratory for teaching me basics of polymer chemistry and synthesis. I am also obliged to Prof. Dr. Duco Jansen, the Director of Graduate Studies in the Department of Biomedical Engineering for his precious guidance and encouragement during my journey towards the master’s degree. I am grateful to the entire Department of Biomedical Engineering for support, especially John Dunbar and Tina Shaw without whom my research would have moved at a snail’s pace! Finally, I would like to thank my parents, whose love and guidance are with me in whatever I pursue. Last but not the least;

I would like to thank all of the people who helped me directly or indirectly during my research. It has been a pleasure to work on my master’s thesis at Vanderbilt!

ii

LIST OF TABLES

Page Table

1. Series of random copolymers with increasing BA content…………………… 46

2. LCST of N-P-B polymers at different pHs…………………………………… 53

3. Parameters a and b obtained from Weibull best fits of the release data……. 57

–  –  –

DEDICATION………………………………………………………………………i ACKNOWLEDGEMENTS…………………………………………………….... ii LIST OF TABLES………………………………………………………………....iii Chapter

1. REVIEW ON MICROSPHERES……………………………………………. 1 Introduction………………………………………………………………. 1 Definition of microspheres……………………………………………….. 1 Utility of microspheres…………………………………………………… 2 Materials used for microsphere fabrication……………………………. 4 Natural polymers…………………………………………………. 4 Synthetic polymers……………………………………………….. 4 Methods of preparing microspheres…………………………………….. 5 Single emulsion method………………………………………….. 6 Double emulsion method………………………………………... 8 Open-closed pores method and Thermoreversible gel method... 10 Parameters considered in characterization of microspheres…………... 12 Particle size………………………………………………………... 12 Drug loading capacity and encapsulation efficiency…………… 13 Type of release profile…………………………… ………………. 15 Mechanisms of drug release from microspheres… …………………….. 16 Degradation ………………………………………………………. 16 Stimuli responsive release…………………………………………18 Applications of microspheres……………………………………………...20 Vaccine delivery……………………………………………………21 Protein delivery…………………………………………………… 22 Nucleotide delivery………………………………………………... 23 Therapeutic and diagnostic magnetic microspheres……………. 23 Microspheres for embolization…………………………………… 24 Diagnostic and therapeutic radioactive microspheres………….. 24 Surface modified microspheres………………………………….. 25 Future scope……………………………………………………….. 26 References…………………………………………………………. 27

2. TEMPERATURE AND PH RESPONSIVE MICROSPHERES FOR SUSTAINED

PROTEIN RELEASE IN ISCHEMIC ENVIRONMENTS……………………37 Introduction……………………………………………………………….. 37 Materials…………………………………………………………………... 39 Methods…………………………………………………………………… 40 Polymer synthesis…………………………………………………. 40 Polymer characterization………………………………………… 41 Microsphere fabrication………………………………………….. 42 Microsphere characterization……………………………………. 44 Release Study……………………………………………………... 45 Results and Discussion…………………………………………………… 46 Conclusion………………………………………………………………... 59 References………………………………………………………………… 60

3. REACTIVE OXYGEN SPECIES SENSITIVE MICROSPHERES FOR





SUSTAINED RELEASE OF CURCUMIN…………………………………… 63 Introduction……………………………………………………………….. 63 Materials……………………………………………………………………66 Methods……………………………………………………………………. 66 Synthesis of poly(propylene sulfide)and characterization………66 Microsphere fabrication…………………………………………. 67 Microsphere characterization…………………………………… 68 Release Study……………………………………………………... 69 Results and Discussion…………………………………………………… 70 Conclusion………………………………………………………………… 78 References…………………………………………………………………. 79

Chapter 1

–  –  –

1.Introduction In recent years, interest in controlled and sustained release of drugs has increased as the pharmaceutical companies seek improved methods of delivering therapeutic dosages of medicines. Benefits to patients would be enhanced if dosages could be sustained for extended periods. Tunable, sustained delivery platforms are therefore necessary to achieve optimal and functional delivery of drugs. Microspheres are one of the widely researched candidates in such delivery platforms. This chapter deals with their advantages, methods of fabrication, characterization techniques, and reviews recent controlled drug release applications using microspheres made from biodegradable and stimuli responsive polymers.

2. Definition of microspheres Microspheres are defined as spherical microscopic particles that range from 1- 1000 um 1, 2 in diameter. They are homogeneous structures made up of a continuous phase of one or more miscible polymers in which particulate drug is dispersed throughout the matrix unlike microcapsules, which have an inner core surrounded by a distinct outer shell5. A wide range of core materials have been encapsulated in microspheres, including

–  –  –

as fillers and bulking agents and even for embolization therapy.4

3.Utility of microspheres The idea of controlled release from polymers dates back to the 1960s through the employment of silicone rubber and polyethylene polymer microcapsules as delivery systems1. However, the requirement of eventual surgical removal because of nondegradability of these systems limited their applicability and urged the need to prepare systems which would be eventually eliminated from the body. Many new delivery systems like liposomes, hydrogels, etc. were designed thereafter and investigated but none emerged as perfect system due to issues with immunogenicity, stability, site and rate of administration, dosage, control over release rates, pharmacokinetics and pharmacodynamics.

In terms of release kinetics, delivery of most drugs, whether by oral administration or through injection, follows what is known as “first-order kinetics” characterized by initial high blood levels of the drugs, followed by exponential fall in blood concentration. This is problematic because once blood concentrations fall below certain levels, no therapeutic effect will be achieved.

Furthermore, some drugs are toxic at high blood level concentrations. It is difficult to achieve a balance between effective levels and toxic levels when blood concentrations fall off so rapidly.

Ideal delivery of drugs would follow “zero-order kinetics”, wherein blood levels of drugs would remain constant throughout the delivery period.

Consequently, scientists have been searching for methods to deliver drugs with zero-order kinetics. An unmet challenge has been to select the best controlled release technology.

Microspheres, with many advantages described below, are on the forefront of this

–  –  –

in single dosage size, a continuous drug release, decrease in systemic side effects, reduced possibility of dose dumping, reduced frequency of administration, and, therefore, increased patient compliance. Non-invasive placement and localized release of desired amount of therapeutic agents, circumvents the deleterious side effects of systemic administration6. This enables administration of larger, effective dosages. Furthermore, the size and size distribution of microspheres can be controlled to achieve a better predicted response. Moreover, microspheres can be manufactured with biodegradable materials or stimuli responsive materials which eliminate the need for device recovery. Because of their ability to act as a device for controlled release drug delivery, microspheres have been used to encapsulate many types of drugs, including small molecules, proteins, and nucleic acids and are easily administered through a syringe needle. They can provide sustained drug release for long periods of time.

On the other hand, disadvantages of microspheres may include difficulty of large scale manufacturing, high cost of manufacturing, and inactivation of drug during fabrication and poor control of drug release rates. Nutropin Depot, which comprised of Genentech’s recombinant human growth hormone (rhGH) encapsulated within poly(D, L-Lactide-co-glycolide) (PLG), was pulled from the market because of high cost of production and manufacturing. Microspheres as fillers and bulking agents tend to migrate away from the injection site, which can cause a loss of therapeutic effects and may also cause embolism, which can eventually lead to organ damage.

–  –  –

4.1 Natural Polymers Natural polymers are of interest because of their biocompatibility, relative abundance and commercial availability, and ease of processing. Natural polymers include alginate, proteins, collagens (gelatin), fibrins, albumin, gluten, elastin, fibroin, hyaluronic acid, cellulose, starch, chitosan (chitin), pectin (pectinic acid), galactan, curdlan, gellan, levan, emulsan, dextran, pullulan, heparin, silk, chondroitin 6-sulfate, polyhydroxyalkanoates, etc. 7

4.2 Synthetic Polymers Synthetic polymers are largely divided into two categories: biodegradable and nonbiodegradable. Biodegradable synthetic polymers include poly(α-hydroxyester)s, polyanhydrides, and polyorthoesters8. Among these, the poly(α-hydroxyester)s such as polylactide (PLA), polyglycolide (PGA), and its copolymers are most extensively used.

These polymers, which are biocompatible, biodegradable, and bioresorbable, are approved by the Food and Drug Administration (FDA) and are also advantageous due to their controlled degradation behavior.

–  –  –

polyhydroxyethymethacrylate (PHEMA), and poly(N-isopropylacrylamide) (PNIPAAm).

Synthetic polymers have an advantage of large scale availability and tunable mechanical and chemical properties.

–  –  –

For preparation of microspheres, certain requirements must be met while choosing an

appropriate encapsulation process10. These are:

1) The biological activity and chemical stability of the incorporated drugs should be maintained as much as possible during the process of encapsulation.

2) The encapsulation efficiency and the yield of the microparticles should be high enough for mass production.

3) The size range of thee microparticles produced should be reasonable (250 um) so that they can be administered using the syringe needle via the parenteral

–  –  –

5) The employed process should produce stable, non-aggregating microparticles, thus making it easy to prepare uniform suspension of microparticles.



Pages:   || 2 | 3 | 4 | 5 |   ...   | 8 |


Similar works:

«E Series on Knots and Everything — Vol. 2 How Surfaces Intersect in Space An introduction to topology Second Edition J Scott Carter World Scientific How Surfaces Intersect in Space SERIES ON KNOTS AND EVERYTHING Editor-in-charge: Louis H. Kauffman Published: Vol. 1: Knots and Physics L. H. Kauffman Vol. 2: How Surfaces Intersect in Space J. S. Carter Quantum Topology Vol. 3: edited by L. H. Kauffman & R. A. Baadhio Gauge Fields, Knots and Gravity Vol. 4: J. Baez & J. P. Muniain Knots and...»

«Processes for developing affordable and sustainable medium-density housing models for greyfield Report precincts Appendix 1 authored by Shane Murray, Nigel Bertram, Lee-Anne Khor, Deborah Rowe, Byron Meyer, Catherine Murphy, Peter Newton, Stephen Glackin, Tom Alves and Rob McGauran for the Australian Housing and Urban Research Institute at Monash University January 2015 ISBN: 978-1-922075-76-5 ACKNOWLEDGEMENTS This material was produced with funding from the Australian Government and the...»

«Comput Econ DOI 10.1007/s10614-014-9465-4 Minimality of State Space Solutions of DSGE Models and Existence Conditions for Their VAR Representation Massimo Franchi · Paolo Paruolo Accepted: 13 August 2014 © European Union 2014 Abstract Standard solution methods of DSGE models do not necessarily deliver minimal state space forms. When the ABCD form is non-minimal, the conditions in the literature are not necessary for the existence of a VAR representation of the observables. In this paper we...»

«4th-year Thesis Projects in Chemistry University of Ontario Institute of Technology Oshawa, Ontario Canada L1H 7K4 February 2016 Table of Contents Page Tenured and Tenure-Track Faculty (TTTF) Prof. Yuri Bolshan...2 Prof. Jean-Paul Desaulniers...3 Prof. Brad Easton...4 Prof. Fedor Naumkin...5 Prof. Liliana Trevani...6 Prof. Olena Zenkina...7 Teaching Faculty (TF) Prof. Marc Adler...9 Dr. Kevin Coulter... 10 Guidelines for Selecting a Thesis Supervisor..11 1|Page Professor Yuri Bolshan, Assistant...»

«The Sophisticate and the Ingénue: Two Visions of la Parisienne in Jacques Deray’s La Piscine. Felicity Chaplin On a balmy summer evening, guests are arriving at a remote villa on the Mediterranean for a night of drinking and dancing. On the terrace the sound of crickets fills the night air. Marianne (Romy Schneider) appears in an iridescent sequined dress, featuring a kaleidoscope of dusty pink, silver blue, bronze and gold. The shimmering v-neck sleeveless dress displays her curvaceous...»

«Heywood, Middleton & Rochdale Glaucoma Repeat Readings Service Heywood, Middleton & Rochdale Glaucoma Repeat Readings Policies and Protocols GM Primary Eyecare Ltd Heywood, Middleton & Rochdale Glaucoma Repeat Readings Service GRRS Contract and Protocol Key Points Each practice has a contract with GM Primary Eyecare Ltd (GMPEC Ltd) to supply services under the Glaucoma Repeat Readings Service (GRR). This contract mirrors the contract between GMPEC LTD and the Clinical Commissioning Group (CCG)....»

«2016-17 APPLICATION Disney Musicals in Schools is an outreach initiative that develops musical theatre programs in New York City public elementary schools through two tiers of programming. The Disney Musicals in Schools: Residency program is perfect for schools without prior theatre experience. The Disney Musicals in Schools: Mini-Residency program is ideal for schools with minimal theatre arts experience. Both programs are designed to spark a tradition of musical theatre in your school! Up to...»

«THE GOALPOST A Shrine Bowl of the Carolinas Publication Page 1 Volume VIII, Issue 2, February 2016 Editor: French Harvey, sbadmin37@shrine-bowl.com The Electronic Newsletter of Shrine Bowl of the Carolinas www.shrine-bowl.com Shrine Bowl of the Carolina’s select coaches for the 80th Game Ron Long, Athletic Director of the Shrine Bowl Of The Carolina’s announced the Coaches selections for the 2016 North Carolina Tar Heels and the South Carolina Sandlappers. These Coaches have been selected...»

«In the United States Court of Federal Claims No. 06-287V March 19, 2007 To be Published ***************************** WILLIAM STEWART and LEONOR SOTELO, * on Behalf of WILLIAM STEWARTSOTELO, * a Minor, * * Petitioners, * * v. * Entitlement; acute cerebellar * ataxia caused by hepatitis A SECRETARY OF THE DEPARTMENT OF * vaccine HEALTH AND HUMAN SERVICES, * * Respondent. * ***************************** Richard Gage, Cheyenne, WY, for petitioners. Robin L. Brodrick, Washington, DC, for...»

«Information for Patients Receiving Radiation Therapy: Head and Neck Cancer Why is radiation therapy used to treat head and neck cancer? Head and neck cancers may be treated with a combination of treatments such as surgery, radiation therapy, and chemotherapy. Radiation Therapy uses radiation from high-energy X-ray machines to kill cancer cells. Radiation is used to shrink cancer or lower the chance of the cancer returning in the head and neck area (and lymph node areas). What will happen on the...»

«Media Kit Photo: Matt Clarke 1 Table of Contents Photo: Matt Clarke Message from Premier Christy Clark 1 Welcome from Andrew Jakubeit, Mayor of the City of Penticton 2 British Columbia Fact Sheet 3 Overview of Penticton 5 Okanagan Wine Country 7 Media Tours 9 Tour Partners 13 Monday Evening Reception Partners 28 Tuesday Evening Reception Partners 30 Our Sponsors 32 A Message from Premier Christy Clark As Premier of the Province of British Columbia, I am pleased to welcome everyone to Penticton...»

«Copyright by Soo-Young Lee 2007 The Dissertation Committee for Soo-Young Lee Certifies that this is the approved version of the following dissertation: God’s Chosen People: Protestant Narratives of Korean Americans and American National Identity Committee: Mark C. Smith, Supervisor Elizabeth Engelhardt Shirley Thompson Nhi Lieu Robert Oppenheim God’s Chosen People: Protestant Narratives of Korean Americans and American National Identity by Soo-Young Lee, B.A.;M.A. Dissertation Presented to...»





 
<<  HOME   |    CONTACTS
2016 www.dissertation.xlibx.info - Dissertations, online materials

Materials of this site are available for review, all rights belong to their respective owners.
If you do not agree with the fact that your material is placed on this site, please, email us, we will within 1-2 business days delete him.