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Sustained presentation of therapeutic factors
Descriptive
TitleInfo
Title
Sustained presentation of therapeutic factors
Name
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Lowe
NamePart
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Christopher J.
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Christopher J. Lowe
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author
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Shreiber
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David I
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David I Shreiber
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Advisory Committee
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chair
Name
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Yarmush
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Martin l
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Martin l Yarmush
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Advisory Committee
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internal member
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(type = personal)
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(type = family)
Freeman
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(type = given)
Joseph W
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Joseph W Freeman
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Advisory Committee
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internal member
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Alder
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Janet
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Janet Alder
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Advisory Committee
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outside member
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Rutgers University
Role
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degree grantor
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School of Graduate Studies
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school
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Text
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theses
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DateCreated
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2018
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2018-10
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2018
Place
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xx
Language
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eng
Abstract
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The 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.
Subject
(authority = RUETD)
Topic
Biomedical Engineering
Subject
(authority = ETD-LCSH)
Topic
Therapeutics
Subject
(authority = ETD-LCSH)
Topic
Pharmacology
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Title
Rutgers University Electronic Theses and Dissertations
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ETD
Identifier
ETD_9173
PhysicalDescription
Form
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electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (110 pages) : illustrations
Note
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Ph.D.
Note
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Includes bibliographical references
Note
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by Christopher J. Lowe
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TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
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rucore10001600001
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
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doi:10.7282/t3-0s3e-jp16
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
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The author owns the copyright to this work.
RightsHolder
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Name
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Lowe
GivenName
Christopher
Role
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RightsEvent
Type
Permission or license
DateTime
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2018-09-03 15:19:41
AssociatedEntity
Name
Christopher Lowe
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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windows xp
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1.7
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2018-09-19T18:19:19
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2018-09-19T18:19:19
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