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Development of a Novel Anti-Infectivity Platform for the Treatment of Neglected Tropical and Infectious Diseases Andrea Marie Binnebose Iowa State University

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Development of a Novel Anti-Infectivity Platform for the Treatment of Neglected Tropical and Infectious Diseases Andrea Marie Binnebose Iowa State University Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2018 Development of a novel anti-infectivity platform for the treatment of neglected tropical and infectious diseases Andrea Marie Binnebose Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Biomedical Commons, and the Microbiology Commons Recommended Citation Binnebose, Andrea Marie, "Development of a novel anti-infectivity platform for the treatment of neglected tropical and infectious diseases" (2018). Graduate Theses and Dissertations. 16318. https://lib.dr.iastate.edu/etd/16318 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]. Development of a novel anti-infectivity platform for the treatment of neglected tropical and infectious diseases by Andrea M. Binnebose A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Microbiology Program of Study Committee: Bryan H. Bellaire Major Professor Balaji Narasimhan Jesse Hostetter Michael J. Wannemuehler Richard Martin The student author, whose presentation of the scholarship herein was approved by the program of study committee, is solely responsible for the content of this dissertation. The Graduate College will ensure this dissertation is globally accessible and will not permit alterations after a degree is conferred. Iowa State University Ames, Iowa 2018 Copyright © Andrea Marie Binnebose, 2018. All rights reserved ii DEDICATION I dedicate this dissertation to the most amazing and influential men in my life. When this journey began so many years ago, I had not realized how quickly my boys would grow. You have become strong and healthy young men and I feel like I have missed so many of your firsts.You have made me stronger, better and more fulfilled than I could have ever imagined. This dissertation is the culmination of our journey towards a Ph.D. which was just like climbing an insurmountable mountain. Together you have walked hand in hand, step by step with me through all the hardships, missed pickup times, just give me ten more minutes, and I have to no idea what you are talking about mom, but that is ok tell me. I love you iii TABLE OF CONTENTS LIST OF FIGURES ......................................................................................................... v LIST OF TABLES ........................................................................................................ vii ACKNOWLEDGMENTS ............................................................................................... x ABSTRACT .................................................................................................................. xii CHAPTER 1 . INTRODUCTION ...................................................................................... 1 CHAPTER 2 . LITERATURE REVIEW ........................................................................... 3 Drug delivery systems ..................................................................................................... 3 Infectious diseases targeted for nanotherapeutic development ....................................... 6 Lymphatic filariasis ..................................................................................................... 6 Mycobacterium .......................................................................................................... 14 References ..................................................................................................................... 31 CHAPTER 3 . POLYANHYDRIDE NANOPARTICLE DELIVERY PLATFORM DRAMATICALLY ENHANCES KILLING OF FILARIAL WORMS ........................................................................................................................... 48 Abstract ......................................................................................................................... 48 Introduction ................................................................................................................... 50 Materials and methods .................................................................................................. 53 Results ........................................................................................................................... 60 Discussion ..................................................................................................................... 70 Conclusions ................................................................................................................... 75 Acknowledgements ....................................................................................................... 76 References ..................................................................................................................... 79 CHAPTER 4 . NANOPARTICLE-BASED DRUG DELIVERY INCREASED SYNERGISM OF FIRST-LINE ANTI-FILARIAL DRUG ACTIVITY AGAINST BRUGIA PAHANGI ....................................................................................... 84 Abstract ......................................................................................................................... 84 Introduction ................................................................................................................... 86 Materials and methods .................................................................................................. 91 iv Results ........................................................................................................................... 97 Confocal Microscopy .................................................................................................. 105 Discussion ................................................................................................................... 108 References ................................................................................................................... 112 CHAPTER 5 . THE EFFECTIVENESS OF A NANO-BASED DELIVERY PLATFORM AGAINST MYCOBACTERIUM MARINUM ........................................... 118 Abstract ....................................................................................................................... 118 Introduction ................................................................................................................. 119 Materials and methods ................................................................................................ 122 Results ......................................................................................................................... 127 Discussion ................................................................................................................... 136 Conclusion ................................................................................................................... 140 References ................................................................................................................... 140 CHAPTER 6 . AMPHIPHILIC POLYANHYDRIDE NANOPARTICLE DRUG DELIVERY PLATFORM EFFECTIVELY KILLS MYCOBACTERIUM AVIUM SUBSPECIES PARATUBERCULOSIS............................................................. 145 Abstract ....................................................................................................................... 145 Introduction ................................................................................................................. 146 Materials and methods ................................................................................................ 148 Results ......................................................................................................................... 153 References ................................................................................................................... 160 CHAPTER 7 . NANOBASED DRUG DELIVERY ENHANCES THE ACTIVITY OF ANTIBIOTIC COCKTAIL AGAINST MULTI-DRUG RESISTANT MYCOBACTERIUM ................................................................................. 164 Abstract ....................................................................................................................... 164 Introduction ................................................................................................................. 165 Materials and methods ................................................................................................ 168 Results ......................................................................................................................... 177 Discussion ................................................................................................................... 189 Conclusion ................................................................................................................... 192 References ................................................................................................................... 193 CHAPTER 8 . CONCLUSIONS AND FUTURE WORK ............................................. 197 References ................................................................................................................... 202 v LIST OF FIGURES Figure
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