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Polymer Chemistry Effects on Protein Release and Immune Activation Senja Katarina Lopac Iowa State University

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Polymer Chemistry Effects on Protein Release and Immune Activation Senja Katarina Lopac Iowa State University Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 2008 Polymer chemistry effects on protein release and immune activation Senja Katarina Lopac Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Polymer Chemistry Commons, and the Polymer Science Commons Recommended Citation Lopac, Senja Katarina, "Polymer chemistry effects on protein release and immune activation" (2008). Retrospective Theses and Dissertations. 14904. https://lib.dr.iastate.edu/rtd/14904 This Thesis is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Polymer chemistry effects on protein release and immune activation by Senja Katarina Lopac A thesis submitted to the graduate faculty in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Major: Chemical Engineering Program of Study Committee: Balaji Narasimhan, Major Professor Michael Wannemuehler Aaron Clapp Iowa State University Ames, Iowa 2008 Copyright © Senja Katarina Lopac, 2008. All rights reserved. UMI Number: 1450148 UMI Microform 1450148 Copyright 2008 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, MI 48106-1346 ii TABLE OF CONTENTS ACKNOWLEDGEMENTS ............................................................................................ vi CHAPTER 1: INTRODUCTION.....................................................................................1 1.1 Introduction ...............................................................................................................1 1.2 References .................................................................................................................4 CHAPTER 2: BACKGROUND AND LITERATURE REVIEW.................................5 2.1 Summary ...................................................................................................................5 2.2 Polyanhydrides..........................................................................................................5 2.2.1 History ................................................................................................................5 2.2.2 Structures............................................................................................................6 2.2.2.1 Aliphatic......................................................................................................6 2.2.2.2 Aromatic .....................................................................................................7 2.2.2.3 Novel polyanhydride...................................................................................7 2.2.2.4 Other ...........................................................................................................8 2.2.3 Synthesis.............................................................................................................9 2.2.3.1 Melt polycondensation................................................................................9 2.2.3.2 Solution polymerization............................................................................10 2.2.3.3 Dehydrative coupling................................................................................11 2.2.3.4 Ring-opening polymerization ...................................................................12 2.2.4 Characterization................................................................................................13 2.2.5 Degradation and erosion...................................................................................15 2.2.6 Polyanhydrides for drug delivery .....................................................................17 2.3 Microspheres ...........................................................................................................18 2.3.1 Fabrication........................................................................................................18 2.3.1.1 Hot-melt microencapsulation....................................................................18 iii 2.3.1.2 Solvent evaporation ..................................................................................19 2.3.1.3 Solvent removal ........................................................................................19 2.3.1.4 Spray drying..............................................................................................20 2.3.2 Characterization................................................................................................21 2.3.3 Release..............................................................................................................22 2.4 Mechanisms of Immune Response..........................................................................23 2.4.1 Innate and adaptive immunity ..........................................................................23 2.4.2 Major histocompatibility complex ...................................................................23 2.4.3 Dendritic cells...................................................................................................25 2.5 Adjuvants and Vaccines..........................................................................................27 2.5.1 Novel therapies using polymers .......................................................................28 2.6 Conclusion...............................................................................................................30 2.7 References ...............................................................................................................32 CHAPTER 3: RESEARCH OBJECTIVES AND ORGANIZATION .......................38 3.1 Research Objectives ................................................................................................38 3.2 Thesis Organization.................................................................................................39 CHAPTER 4: EFFECT OF POLYMER CHEMISTRY AND FABRICATION METHOD ON PROTEIN RELEASE AND STABILITY FROM POLYANHYDRIDE MICROSPHERES ..................................................................40 4.1 Abstract ...................................................................................................................40 4.2 Introduction .............................................................................................................41 4.3 Materials and Methods ............................................................................................44 4.3.1 Materials...........................................................................................................44 4.3.2 Monomer/polymer synthesis ............................................................................44 iv 4.3.3 Protein...............................................................................................................45 4.3.4 Contact angle measurements ............................................................................45 4.3.5 Microsphere fabrication methods.....................................................................46 4.3.5.1 Solid-oil-oil emulsion ...............................................................................46 4.3.5.2 Cryogenic atomization..............................................................................47 4.3.6 Microsphere characterization ...........................................................................48 4.3.7 Ova release .......................................................................................................49 4.3.8 Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).....50 4.3.9 Western blot......................................................................................................51 4.4 Results .....................................................................................................................52 4.4.1 Contact angle....................................................................................................52 4.4.2 Release of ovalbumin from polyanhydride microspheres................................53 4.4.3 SDS-PAGE.......................................................................................................56 4.4.4 Western blot......................................................................................................58 4.5 Discussion ...............................................................................................................59 4.6 Conclusion...............................................................................................................62 4.7 Acknowledgements .................................................................................................62 4.8 References ...............................................................................................................63 CHAPTER 5: EFFECT OF POLYMER CHEMISTRY ON IMMUNE ACTIVATION OF DENDRITIC CELLS.................................................................67 5.1 Introduction .............................................................................................................67 5.2 Materials
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