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The utility of L-tyrosine based polycarbonate copolymers containing poly(ethylene glycol) as a degradable carrier for the release of a hydrophobic peptide molecule

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TypeOfResource
Text
TitleInfo (ID = T-1)
Title
The utility of L-tyrosine based polycarbonate copolymers containing poly(ethylene glycol) as a degradable carrier for the release of a hydrophobic peptide molecule
SubTitle
PartName
PartNumber
NonSort
Identifier (displayLabel = ); (invalid = )
ETD_2057
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000051844
Language (objectPart = )
LanguageTerm (authority = ISO639-2); (type = code)
eng
Genre (authority = marcgt)
theses
Subject (ID = SBJ-1); (authority = RUETD)
Topic
Biomedical Engineering
Subject (ID = SBJ-2); (authority = ETD-LCSH)
Topic
Eye--Diseases--Treatment
Subject (ID = SBJ-3); (authority = ETD-LCSH)
Topic
Drug delivery systems
Abstract
The utility of biodegradable polymers as localized drug delivery carriers is an ongoing area of research where investigators attempt to deliver a wide range of hydrophobic small molecules and peptides. The long-term (> 1 year), controllable and sustained release of such molecules from these solid carriers has not been demonstrated due to the complexity of the reaction-diffusion mechanisms that occur in these hydrated polymers. The goal of the present research was to characterize the release of the hydrophobic peptide voclosporin from a class of biodegradable amorphous polymers based on desaminotyrosyl-tyrosine alkyl ester (DTR) and desaminotyrosyl-tyrosine ester, (DT), and the monomer polyethylene glycol (PEG). Four areas of study were presented: (i) the modulation of drug release and polymer erosion as a function of poly(DTR-co-y % DT-co-z % PEG1K carbonate) homo-, co- and terpolymer compositions, (ii) the changes in polymer morphology and a proposed theory to account for drug retention exhibited by these polymers after prolonged hydration, (iii) the instability of voclosporin in the presence of the terpolymer carriers and the need for formulations containing antioxidants and (iv) the demonstration of selected PEG-containing polycarbonate formulations as a drug delivery vehicle for potential ophthalmic applications. The polycarbonate terpolymers were shown to undergo hydration-induced microphase separation, where the mobility of the PEG1K length in the composition enabled this behavior. The limited access of water to regions containing only PEG was believed to cause both drug retention and a slowdown in polymer erosion in these matrices. Drug-polymer interaction between DTE-co-DT segments of the polymer and voclosporin was also suspected to play a role in drug retention. In vivo in vitro correlation (IVIVC) values of 3 to 4 obtained from rabbit implantation studies implied that both drug release and polymer resorption would be enhanced if these carriers were placed within the human body. Select tyrosine-based polycarbonate terpolymer matrices were well tolerated in the sensitive regions of the rabbit’s eye. An outcome of this research is the development of a polymer platform that can serve as an implantable medical device matrix to deliver drugs to patients for the treatment of chronic diseases and disorders of the eye.
PhysicalDescription
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electronic resource
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xxxii, 188 p. : ill.
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application/pdf
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Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references (p. 183-187)
Note (type = statement of responsibility)
by Isaac John Khan
Name (ID = NAME-1); (type = personal)
NamePart (type = family)
Khan
NamePart (type = given)
Isaac John
NamePart (type = date)
1965-
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author
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Isaac John Khan
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Kohn
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Joachim
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chair
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Advisory Committee
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Joachim Kohn
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Shreiber
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David
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internal member
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Advisory Committee
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David I Shreiber
Name (ID = NAME-4); (type = personal)
NamePart (type = family)
Shinbrot
NamePart (type = given)
Troy
Role
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internal member
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Advisory Committee
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Troy Shinbrot
Name (ID = NAME-5); (type = personal)
NamePart (type = family)
Velagaleti
NamePart (type = given)
Poonam
Role
RoleTerm (authority = RULIB); (type = )
outside member
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Advisory Committee
DisplayForm
Poonam Velagaleti
Name (ID = NAME-1); (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB); (type = )
degree grantor
Name (ID = NAME-2); (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB); (type = )
school
OriginInfo
DateCreated (point = ); (qualifier = exact)
2009
DateOther (qualifier = exact); (type = degree)
2009-10
Place
PlaceTerm (type = code)
xx
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/T33778W2
Genre (authority = ExL-Esploro)
ETD doctoral
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RightsDeclaration (AUTHORITY = GS); (ID = rulibRdec0006)
The author owns the copyright to this work
Copyright
Status
Copyright protected
Notice
Note
Availability
Status
Open
Reason
Permission or license
Note
RightsHolder (ID = PRH-1); (type = personal)
Name
FamilyName
Khan
GivenName
Isaac
Role
Copyright holder
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Permission or license
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Place
DateTime
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Name
Isaac Khan
Affiliation
Rutgers University. Graduate School - New Brunswick
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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.
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