microdermabrasion for transdermal drug delivery

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  • MICRODERMABRASION FOR TRANSDERMAL DRUG DELIVERY

    A Thesis

    Presented to

    The Academic Faculty

    by

    Samantha N. Andrews

    In Partial Fulfillment

    of the Requirements for the Degree

    Doctor of Philosophy in Biomedical Engineering

    in the

    The Wallace H. Coulter Department of Biomedical Engineering

    Georgia Institute of Technology

    December 2010

    COPYRIGHT 2010 by Samantha N. Andrews

  • ii

    MICRODERMABRASION FOR TRANSDERMAL DRUG DELIVERY

    Approved by:

    Dr. Mark Prausnitz, Advisor Dr. Julia Babensee

    School of Chemical Engineering & Biomolecular

    Engineering

    Wallace H. Coulter Department of Biomedical

    Engineering

    Georgia Institute of Technology Georgia Institute of Technology

    Dr. Gilda Barabino Dr. Niren Murthy

    Wallace H. Coulter Department of Biomedical

    Engineering

    Wallace H. Coulter Department of Biomedical

    Engineering

    Georgia Institute of Technology Georgia Institute of Technology

    Dr. Richard Compans Dr. Eric Tomlinson

    Emory School of Medicine Altea Therapeutics

    Emory University

    Date Approved: August 17, 2010

  • iii

    To my mother,

    whose tireless sacrifices continue to inspire me everyday

  • iv

    ACKNOWLEDGEMENTS

    I would like to thank my advisor, committee members, and funding sources for making it

    possible for me to carry out my thesis work. Thanks to Dr. Mark Prausnitz for serving as a great

    mentor and for guiding me through graduate school. I would also like to thank my thesis

    committee members, Dr. Barabino, Dr. Tomlinson, Dr. Murthy, Dr. Babensee, and Dr. Compans,

    for their support, feedback, and suggestions for my project.

    Many thanks to all the members of the Prausnitz lab, past and present, for all their

    guidance, and support in help me to complete my project. I will cherish the great laughs,

    friendships, cultural lessons, lab socials, and conferences. Dr. Harvinder Gill was instrumental in

    getting me started on my project. His mentoring helped me to start a project in which I had no

    prior experience. Dr. Jeong Woo Lee and Dr. Seong-O Choi, my Dream Team, were always

    willing to assist me with my in vivo studies and ELISA. Thanks to Dr. Yue-Chun Kim and Aritra

    Sengupta for helping with the in vitro delivery study and Dr. Tanicia Daley for supplying insulin.

    Dr. Vladimir Zarnitsyn was instrumental in helping me with designing and fabricating the masks

    for my project. Samir Patel was always willing to assist with the education outreach demos and

    tissue harvesting. I am sure we both scared a few kids out of science, at least not intentionally.

    Dr. Prerona Chakravarty and Ying Liu, my lab sisters, thanks for all the fun times we spent

    together from the road trips, to the trips to Vortex and Macys, and of course teriyaki chicken.

    Thanks to Dr. Hyo-Jick Choi, Yoo Chun Kim, James Norman, Dr. Leonard Chu, Chris Edens,

    Dr. Saffar Moonsor, Dr. Robyn Schlicher, Dr. Jyoti Gupta, and Dr. Cetin Tas for your support

    and guidance during my time as a graduate student.

  • v

    I would like to thank my undergraduate students Eunhye (Grace) Jeong, Brian Bondy,

    and Samantha Koncal for their assistance with my project. I appreciate their enthusiasm,

    dedication, and all their histology sectioning. Thanks to Brian Bondy for counting the hundreds

    of particle for the velocity measurements. It was a pleasure working with all of them.

    I would like to extend gratitude to Donna Bondy, our lab assistant. Without her, our lab

    would be chaotic. Thanks to Donna for being organized, caring, and for baking goodies for the

    lab.

    Thanks to the members of the Compans lab for their help with the in vivo vaccine study.

    Their research and assay expertise was invaluable in helping to carry out the experiment. Special

    thanks to Dr. Dimitrios Koutsonanos and Dr. Ioanna Skountzou for their advice and support of

    my thesis.

    Thanks to Altea Therapeutics for enhancing my graduate school experience by allowing

    me to intern at the company. It was a good learning experience and provided a great introduction

    into preclinical research at a start up company. I am grateful for their support of my thesis work

    and for giving me an opportunity to work in an industrial position.

    Thanks to the IBB staff and core facilities for their help in the completion of my project.

    Thanks to Tracey Couse and Aqua Ashberry for helping with histology. I appreciate their help in

    training, performing immunohistochemistry, and their friendship. Thanks to Steve Woodward for

    maintaining all the core facilities and for helping with training. Lastly I would like to thank the

    IBB administrative staff for their help with packages and letting me in the lab when I couldnt

    find my Buzz Card.

    Thanks to my University of Florida engineering family. Dr. Jonathan F.K. Earle thanks

    for taking a chance on the girl from the Florida Panhandle and for making it your personal

  • vi

    mission to help UF minority engineering students complete their degrees. Thanks for making

    sure I did not get sidetracked at UF and for reminding me that engineering is an obligation, not a

    sacrifice. Thanks to UF NSBE, Mrs. Margie Williams, Mr. Earl Wade for encouraging me to

    attend graduate school and for their support during my time at Georgia Tech.

    Last, but not least I would like to thank my family, especially my mother and brothers,

    for their prayers and words of encouragement. Thanks to my mother, Danita Sheffield, for being

    my biggest cheerleader during highs and lows of graduate and for reminding me that I can

    preserve through anything. Thanks to my brothers, Eddie, Cornelius, Quinn, and Quentin, for

    being great supporters and for not asking why graduate school takes so long to complete.

  • vii

    Table of Contents

    ACKNOWLEDGEMENTS ........................................................................................................ iv

    LIST OF TABLES ........................................................................................................................ x

    LIST OF FIGURES ..................................................................................................................... xi

    LIST OF SYMBOLS AND ABBREVIATIONS ..................................................................... xvi

    CHAPTER 1: INTRODUCTION ................................................................................................ 1

    CHAPTER 2: BACKGROUND .................................................................................................. 3

    Transdermal Drug Delivery ..................................................................................................... 3

    Skin Anatomy/Barrier Properties ........................................................................................... 5

    Microdermabrasion .................................................................................................................. 7

    Skin Mechanical Properties ................................................................................................... 11

    Vaccine Delivery and Immunity ............................................................................................ 11

    Skin Resealing after Injury .................................................................................................... 14

    CHAPTER 3: MATERIAL AND METHODS ........................................................................ 16

    Controlled Pore Formation in Stratum Corneum Using Microdermabrasion ................. 16

    Microdermabrasion Procedure .............................................................................................. 16

    Abrasion Depth Quantification ............................................................................................. 18

    Microdermabrasion Using a Skin Mask ............................................................................... 19

    Statistical Analysis ................................................................................................................ 20

    Transdermal Delivery of Macromolecules Using Microdermabrasion ............................. 21

    Abrasion Protocol ................................................................................................................. 21

    Sulforhodamine Delivery ...................................................................................................... 21

    Bovine Serum Albumin Delivery ......................................................................................... 22

    Inactivated Influenza Vaccine Delivery ................................................................................ 23

    Mask Delivery Study ............................................................................................................ 24

    Transdermal Insulin Delivery Using Microdermabrasion ................................................. 26

    Microdermabrasion Protocol ................................................................................................ 26

  • viii

    Diabetes Induction Protocol .................................................................................................. 27

    Insulin delivery protocol .......................................

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