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Sustained presentation of therapeutic factors
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Lowe, Christopher J.. Sustained presentation of therapeutic factors. Retrieved from https://doi.org/doi:10.7282/t3-0s3e-jp16

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TitleSustained presentation of therapeutic factors
NameLowe, Christopher J. (author); Shreiber, David I (chair); Yarmush, Martin l (internal member); Freeman, Joseph W (internal member); Alder, Janet (outside member); Rutgers University; School of Graduate Studies
Date Created2018
Other Date2018-10 (degree)
SubjectBiomedical Engineering, Therapeutics, Pharmacology
Extent1 online resource (110 pages) : illustrations
DescriptionThe continued development of complex protein therapeutics as life saving medicines has greatly improved outcomes and quality of life for countless patients. Unfortunately, these large complex proteins are not as stable as traditional small molecule drugs and are most commonly administered intravenously, placing burdens on patients who depend on regular dosing. To alleviate these burdens, alternative methods of sustaining therapeutically relevant doses of medicines at sites of injury or disease must be investigated. This dissertation proposes and explores novel methods of sustaining the presentation of therapeutic factors and targeting them to injured and diseased tissues by using native free radicals as a homing signal. Elevated concentrations of free radicals are a characteristic comorbidity of many different injury and disease conditions. In polymer chemistry, free radicals are frequently used to initiate crosslinking and polymerization reactions. We hypothesize that the free radicals characteristic of injured and diseased tissues are capable of inducing crosslinking of acrylate groups. By using acrylated polymers, such as polyethylene glycol diacrylate (PEGDA), coupled to therapeutic factors, this allows for specific targeting and immobilization of these therapeutic factors to injured or diseased tissues with elevated concentrations of free radicals. Further, the interaction of free radicals may reduce or sequester free radicals, limiting their ability to further damage the tissue. Reactive oxygen species (ROS) initiated crosslinking of acrylated PEGs, which enabled the immobilization of a fluorescent payload within tissue mimics. The crosslinking efficiency and immobilization potential varied with the polymer chain length, which suggests that a tunable platform can be achieved. Thiol and alkene functionalized PEGs also demonstrated good crosslinking potential with native free radicals and offer an additional avenue of platform customization. Additionally, the reaction of these functionalized PEGs with free radicals protected cells from the damaging effects of oxidative stress in vitro. Together these results provide promising proof of concept for using free radicals as a means of specifically targeting and sustaining drugs to injured or diseased tissues. Overall the work described in this dissertation has the potential to serve as the building block for improved strategies for administering complex therapeutics to patients in need.
NotePh.D.
NoteIncludes bibliographical references
Noteby Christopher J. Lowe
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/t3-0s3e-jp16
Languageeng
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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