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Hydrogels for Wound Dressings a Thesis Su UNIVERSITY OF CALIFORNIA Los Angeles Drug Release Kinetics from Poly(ethylene glycol) Hydrogels for Wound Dressings A thesis submitted in partial satisfaction of the requirements for the degree Master of Science in Bioengineering by Kaitlyn Alexis Cook 2020 ã Copyright by Kaitlyn Alexis Cook 2020 ABSTRACT OF THESIS Drug Release Kinetics from Poly(ethylene glycol) Hydrogels for Wound Dressings by Kaitlyn Alexis Cook Master of Science in Bioengineering University of California, Los Angeles, 2020 Professor Andrea Kasko, Chair Prolonged field care (PFC) for treatment of battlefield and trauma injuries requires the advancement of wound management techniques in order to prevent loss of life or limb prior to hospitalization in austere combat locations where medical evacuation is delayed. The goal of this project is to design a hydrogel wound dressing capable of providing sustained release of antibiotics, analgesics, and hemostatic agents over a three-day period. Poly(ethylene glycol) (PEG) hydrogels were fabricated through crosslinking using redox initiators – ammonium persulfate (APS) and tetramethylethylene diamine (TEMED). Hydrogels were characterized through the mass swelling ratio (qm) to determine the mesh size (ξ) and thus qualitatively predict the release kinetics of the therapeutic drugs. Hydrogels with incorporated therapeutic drug were placed in known volumes of deionized water, from which aliquots were taken at set ii time intervals. A UV Visible Spectrophotometer determined the aliquots’ absorbance which determined the cumulative release kinetics. Ultimately, three-day sustained release of the therapeutic drugs from the PEG hydrogel was achieved through retarding the diffusion of the therapeutic drugs by incorporating acrylic acid. iii The thesis of Kaitlyn Alexis Cook is approved. Nicholas Bernthal Stephanie Seidlits Andrea Kasko, Committee Chair University of California, Los Angeles 2020 iv I would like to dedicate this thesis to my parents, Matthew and Catherine Cook, who have given me a passion and desire for continuous learning. Thank you for the endless knowledge and support you have provided throughout my academic career. Thanks to my siblings, Madison, Allison, and Keegan, who always challenge me to be better. My family’s competitive nature has held me accountable and pushed me to be my absolute best. I love you all! The day I stop learning is the day I stop growing. I continue to learn to continue to grow. The cream will always rise to the top, it just takes time to get there. v Table of Contents List of Figures .................................................................................................................................................... viii List of Tables ....................................................................................................................................................... xi List of Symbols and Acronyms ............................................................................................................................ xii Acknowledgements ............................................................................................................................................ xv 1 Background ................................................................................................................................................. 1 1.1 Focus Area .................................................................................................................................................. 1 1.2 The Needs of the Military ........................................................................................................................... 3 1.3 Hydrogels as Wound Dressing ................................................................................................................... 7 1.4 Hydrogels for Drug Delivery ..................................................................................................................... 12 1.4.1 Molecular Size ..................................................................................................................................... 12 1.4.2 Crosslink Density ................................................................................................................................. 13 1.4.3 Method of Therapeutic Drug Sequestration ....................................................................................... 14 1.4.4 Therapeutic Drug Concentration and Phase ....................................................................................... 15 1.5 Objective of this Work .............................................................................................................................. 16 1.6 Overview .................................................................................................................................................. 16 2 Computational Modeling ........................................................................................................................... 18 2.1 Background .............................................................................................................................................. 18 2.2 Calculations for Mesh Size ....................................................................................................................... 18 2.3 Calculations for Diffusion from Hydrogel ................................................................................................. 21 2.4 Calculations for SumMation of Therapeutic Drug Released from a Thin FilM .......................................... 23 2.5 Cumulative Release Graphs ..................................................................................................................... 24 2.6 Conclusions .............................................................................................................................................. 28 3 Materials and Methods ............................................................................................................................. 29 3.1 Materials .................................................................................................................................................. 29 3.2 PEG Diacrylate Synthesis .......................................................................................................................... 30 3.3 Hydrogel Preparation ............................................................................................................................... 31 3.4 Characterization ....................................................................................................................................... 33 3.4.1 Volumetric Swelling Ratio (Q) ............................................................................................................. 33 3.4.2 Elastic Modulus (E) .............................................................................................................................. 34 3.4.3 Mesh Size (x) ....................................................................................................................................... 35 3.5 Release Kinetics using UV Visible Spectrometer ....................................................................................... 37 3.5.1 Therapeutic Drug Calibration Curves .................................................................................................. 37 3.5.2 Individual Therapeutic Drug Release Kinetic Studies .......................................................................... 39 3.6 Extended Therapeutic Drug Release using Sodium Polyacrylate ............................................................. 40 3.7 Extended Therapeutic Drug Release using Acrylic Acid ............................................................................ 40 vi 4 Results and Discussion .............................................................................................................................. 42 4.1 Hydrogel Gelation .................................................................................................................................... 42 4.2 Characterization ....................................................................................................................................... 46 4.2.1 Mass Swelling Ratio (q) ....................................................................................................................... 46 4.2.2 Volumetric Swelling Ratio (Q) ............................................................................................................. 48 4.2.3 Elastic Modulus (E) .............................................................................................................................. 49 4.2.4 Mesh Size (ξ) ....................................................................................................................................... 51 4.3 Therapeutic Drug Release Kinetics ........................................................................................................... 53 4.3.1 Calibration Curve ................................................................................................................................. 54 4.3.2 Therapeutic Drug Stock Solutions ....................................................................................................... 57 4.3.3 Individual Therapeutic Drug Release .................................................................................................. 58 4.4 Extended
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