Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2011 Combinatorial design and development of biomaterials for use as drug delivery devices and immune adjuvants Latrisha Kay Petersen Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Biological Engineering Commons, and the Chemical Engineering Commons Recommended Citation Petersen, Latrisha Kay, "Combinatorial design and development of biomaterials for use as drug delivery devices and immune adjuvants" (2011). Graduate Theses and Dissertations. 11988. https://lib.dr.iastate.edu/etd/11988 This Dissertation 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 Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Combinatorial design and development of biomaterials for use as drug delivery devices and immune adjuvants by Latrisha Kay Petersen A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Chemical Engineering Program of Study Committee: Balaji Narasimhan, Major Professor Michael J. Wannemuehler Jennifer O’Donnell Krishna Rajan Ian Schneider Iowa State University Ames, Iowa 2011 Copyright© Latrisha Kay Petersen, 2011. All rights reserved. ii Table of Contents List of Figures ........................................................................................................................ ix List of Tables ..................................................................................................................... xviii Acknowledgments ................................................................................................................ xix Abstract ............................................................................................................................... xxiii Chapter 1: Introduction ..........................................................................................................1 1.1 Introduction ..........................................................................................................................1 1.2 References ............................................................................................................................5 1.3 List of Figures ......................................................................................................................9 Chapter 2: Literature Review ...............................................................................................10 2.1 Summary ............................................................................................................................10 2.2 Polymeric Biomaterials: Drug Delivery Applications .......................................................11 2.2.1 Introduction .............................................................................................................11 2.2.2 Acid-Catalyzed Polymers ........................................................................................13 2.2.3 Polyesters .................................................................................................................14 2.2.4 Polyethers ................................................................................................................16 2.2.5 Polyanhydrides ........................................................................................................17 2.3 Polymeric Biomaterials: Vaccine Adjuvants .....................................................................21 2.3.1 Introduction .............................................................................................................21 2.3.2 Acid-Catalyzed Polymer Adjuvants ........................................................................25 2.3.3 Polyester Adjuvants .................................................................................................27 2.3.4 Polyether Adjuvants ................................................................................................30 iii 2.3.5 Polyanhydride Adjuvants ........................................................................................31 2.4 Combinatorial Design of Biomaterials for Drug Delivery: Opportunities and Challenges ................................................................................................................................34 2.4.1 Introduction .............................................................................................................34 2.4.2 Combinatorial Biomaterial Library Fabrication and Characterization ....................37 2.4.3 High Throughput Cell-based Screening ..................................................................41 2.4.4 Combinatorial Drug Release ...................................................................................46 2.4.5 Expert Opinion ........................................................................................................46 2.4.6 Conclusions .............................................................................................................48 2.5 References ..........................................................................................................................49 2.6 List of Figures ....................................................................................................................65 2.7 List of Tables .....................................................................................................................71 Chapter 3: Research Objectives ...........................................................................................72 Chapter 4: A Novel, High Throughput Method to Study In Vitro Protein Release from Polymer Nanospheres ...................................................................................................74 4.1 Abstract ..............................................................................................................................75 4.2 Introduction ........................................................................................................................75 4.3 Materials and Methods .......................................................................................................78 4.4 Results and Discussion ......................................................................................................82 4.5 Conclusions ........................................................................................................................86 4.6 Acknowledgements ............................................................................................................87 4.7 References ..........................................................................................................................87 4.8 List of Figures ....................................................................................................................91 iv 4.9 List of Tables .....................................................................................................................94 Chapter 5: High Throughput Analysis of Protein Stability in Polyanhydride Nanoparticles ..........................................................................................................................95 5.1 Abstract ..............................................................................................................................96 5.2 Introduction ........................................................................................................................96 5.3 Materials and Methods .....................................................................................................100 5.4 Results and Discussion ....................................................................................................105 5.5 Conclusions ......................................................................................................................114 5.6 Acknowledgements ..........................................................................................................114 5.7 References ........................................................................................................................115 5.8 List of Figures ..................................................................................................................117 5.9 List of Tables ...................................................................................................................121 Chapter 6: Amphiphilic Polyanhydride Nanoparticles Stabilize Bacillus Anthracis Protective Antigen ................................................................................................................123 6.1 Abstract ............................................................................................................................124 6.2 Introduction ......................................................................................................................124 6.3 Materials and Methods .....................................................................................................127 6.4 Results ..............................................................................................................................134 6.5 Discussion ........................................................................................................................139