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Title page for ETD etd-12072017-164241


Type of Document Dissertation
Author Lockhart, Jacob Nathaniel
Author's Email Address jacob.n.lockhart@gmail.com
URN etd-12072017-164241
Title Synthesis of Nanomaterials and Macromolecular Architectures for Dual Drug Delivery Systems, Biosensors, and Antimicrobial Films
Degree PhD
Department Chemistry
Advisory Committee
Advisor Name Title
Eva M. Harth, Ph.D. Committee Chair
John A. McLean, Ph.D. Committee Member
Scott A. Guelcher, Ph.D. Committee Member
Steven D. Townsend, Ph.D Committee Member
Keywords
  • polyglycidol
  • biosensors
  • thin film coatings
  • nanomedicine
  • nanomaterials
Date of Defense 2017-12-05
Availability restrictone
Abstract
Recent progress in nanotechnology has enabled rapid expansion at the interface of polymeric systems and biomedicine such that synthetic nanocarriers can be capable of entrapment and tunable releases of chemotherapeutics, improved potential bioavailability and tumor targeting, as well as anti-cancer effects. It has also been shown that chemotherapy by itself is not sufficient to effectively eradicate cancer cells because they can mutate rapidly. Combination therapies which use hydrophobic and hydrophilic protein therapeutics have gained incredible traction in clinical treatments such as combined chemo-immunotherapy, particularly in malignant and drug-resistant cancers. Along with the delivery of biologicals, the need to stabilize biologically active of enzymes in biosensor applications has grown significantly in the last decade. Another pressing biomedical concern is infections that form from biofilm growth on newly implanted hip and knee replacements. A highly advanced and emerging biocompatible polymer called poly(glycidol), also known as poly(glycerol), has a similar polyether backbone to PEG. However, the branching and multiple hydroxyl groups in its chemical structure enable more versatility for bioconjugations, higher hydrophilicity, and outstanding potential in numerous biomedical nanomaterials, biosensing and surface coating applications. Cationic ring-opening polymerizations have been utilized to synthesize poly(glycidols) and poly(esters) as macromolecular building blocks for nano and macro architectures. The poly(ester) polymers were employed for the synthesis of nanosponges and investigated for sustained dual hydrophobic drug delivery and regulated metabolism. Poly(gycidol) architectures were employed for the genesis of a novel nanogel carriers for sustained combination delivery with small hydrophobic and large hydrophilic therapeutics. Through these investigations, poly(glycidol) was employed for a biosensing platform that can immobilize multiple functioning enzymes for improved detection and reusability, and a hydrogel coating was developed to potentially reduce the growth of microbial infections for hip-and knee implants.
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