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Molecular-size effects of poly(ethylene glycol) doxorubicin nanocarriers on the intraductal treatment of ductal carcinoma in situ (dcis)

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TitleInfo
Title
Molecular-size effects of poly(ethylene glycol) doxorubicin nanocarriers on the intraductal treatment of ductal carcinoma in situ (dcis)
Name (type = personal)
NamePart (type = family)
Gu
NamePart (type = given)
Zichao
NamePart (type = date)
1985-
DisplayForm
Zichao Gu
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Sinko
NamePart (type = given)
Patrick
DisplayForm
Patrick Sinko
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Michniak
NamePart (type = given)
Bozena
DisplayForm
Bozena Michniak
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Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
You
NamePart (type = given)
Guofeng
DisplayForm
Guofeng You
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Love
NamePart (type = given)
Susan
DisplayForm
Susan Love
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (encoding = w3cdtf); (qualifier = exact)
2015
DateOther (qualifier = exact); (type = degree)
2015-01
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2015
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Systemic chemotherapy is not a first-line treatment option for early stage breast cancer due primarily to the limited blood supply in mammary ducts and the variable and limited drug concentration reaching to the tumor within the ducts. To enhance local drug concentration and avoid excess systemic exposure, an intraductal approach for delivering the anti-cancer agents directly to mammary glands provides an alternative method for treating DCIS. Doxorubicin (DOX) is a widely used anti-cancer drug but it rapidly diffuses from the mammary gland into the systemic circulation. Therefore, techniques for retaining drugs locally in the mammary gland are needed. The objective of this thesis project is to design, develop, and evaluate breast intraductal drug delivery systems that provide higher drug retention in the mammary gland, thereby minimizing systemic exposure and achieving maximal local therapeutic effect. PEG polymers with different molecular weights (5, 10, 20 and 40 kDa) and molecular architectures (linear, four-arm and eight-arm) were conjugated to DOX to develop PEG DOX (PEG-DOX) nanocarriers. The hydrodynamic radii studies showed the hydrodynamic radii increased with increasing molecular weight for the linear PEGs and decreased with increased branching in the polymer structure. The mammary gland retention half-lives demonstrated the influence of molecular weight and structure of nanocarriers on mammary gland retention. Pharmacokinetic profiles indicated that nanocarriers with longer retention half-life tend to distribute into the blood stream with a delayed plasma peak time. Histological studies showed no local damage or inflammation in the nanocarrier treated mammary gland, but altered ductal structure was observed in DOX treated mammary gland. A F344 tumor model, developed by inoculating 13762 Mat B III cells into female F344 rats intraductally, exhibited cell load- and time-dependent tumor development in the rats. Efficacy studies demonstrated slower tumor growth in the intraductal treatment groups than in the intravenous treatment groups. The survival rate in the intraductal treatment groups was significant higher than the untreated group. In summary, the developed PEG-DOX nanocarriers improved DOX retention and reduced DOX toxicity in mammary gland, leading to a significantly improved survival percentage in treating DCIS in a F344 tumor rat model.
Subject (authority = RUETD)
Topic
Pharmaceutical Science
Subject (authority = ETD-LCSH)
Topic
Polyethylene glycol
Subject (authority = ETD-LCSH)
Topic
Breast--Cancer
Subject (authority = ETD-LCSH)
Topic
Drug delivery systems
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_6127
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xiv, 119 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Zichao Gu
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3FJ2JG9
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Gu
GivenName
Zichao
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2014-12-30 19:38:46
AssociatedEntity
Name
Zichao Gu
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
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.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2015-01-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2017-01-30
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after January 30th, 2017.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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RULTechMD (ID = TECHNICAL1)
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ETD
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windows xp
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