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PH-responsive amphiphilic macromolecules for anticancer drug and siRNA delivery
Descriptive
TitleInfo
Title
PH-responsive amphiphilic macromolecules for anticancer drug and siRNA delivery
Name
(type = personal)
NamePart
(type = family)
Gu
NamePart
(type = given)
Li
NamePart
(type = date)
1987-
DisplayForm
Li Gu
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
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(type = family)
Uhrich
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(type = given)
Kathryn
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Kathryn Uhrich
Affiliation
Advisory Committee
Role
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chair
Name
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Warmuth
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Ralf
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Ralf Warmuth
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Advisory Committee
Role
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(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
O'Carroll
NamePart
(type = given)
Deirdre
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Deirdre O'Carroll
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Roth
NamePart
(type = given)
Charles
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Charles Roth
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
outside member
Name
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NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB)
degree grantor
Name
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NamePart
Graduate School - New Brunswick
Role
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(authority = RULIB)
school
TypeOfResource
Text
Genre
(authority = marcgt)
theses
OriginInfo
DateCreated
(qualifier = exact)
2014
DateOther
(qualifier = exact);
(type = degree)
2014-01
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Amphiphilic macromolecules (AMs), composed of a macromolecular hydrophobic segment and a hydrophilic poly(ethylene glycol) (PEG) are used as drug delivery systems and therapeutics. In this dissertation, AMs maintained physicochemical and biological properties after commercial sterilization treatment indicating AMs are suitable for commercialization. Furthermore, AMs are modified for anticancer drug and siRNA delivery. In this dissertation, pH-sensitive AMs were successfully synthesized to solve the dilemma between stability during circulation and quick drug release at target site. Critical micelle concentrations of the pH-sensitive AMs indicated stability against dilution which occurs during blood circulation. Doxorubicin (DOX) was chosen as the anticancer drug to investigate the pH-dependent drug release profile. Enhanced DOX release at pH 5 was compared to pH 7.4 due to the cleavage of hydrazone in the AM backbone. Further cytotoxicity studies showed that pH-senstive AMs decreased cell viability compared to free DOX and controll micelles. Therefore, the pH-sensitive AMs can achieve both stability in physiological condition and quick drug release at target site. The delivery of short interfering ribonucleic acid (siRNA), a potent gene knock-down therapeutic, is a main issue in biomedical field. In this dissertation, novel cationic amphiphilic macromolecule (CAM)-lipid complexes were developed with comparable transfection efficiency to Lipofectamin, a gold standard siRNA delivery vehicle in vitro. Dynamic light scattering indicated that CAM-lipid complexes possess the pH-responsive features: stable at pH 7.4 (physiological pH) and instable at pH 5 (endosomal pH). Intracellular trafficking demonstrated the endosomal escape of siRNA possibly because of the pH-responsive feature. Furthermore, this dissertation is the first example of using isothermal titration calorimetry to study siRNA release from polymer-liposome systems. Overall, CAM-lipid complex was developed as an efficient siRNA carrier in vitro and mechanistic insights in delivery process provided.
Subject
(authority = RUETD)
Topic
Chemistry and Chemical Biology
Subject
(authority = ETD-LCSH)
Topic
Macromolecules
Subject
(authority = ETD-LCSH)
Topic
Drug delivery systems
Subject
(authority = ETD-LCSH)
Topic
Cancer--Treatment
RelatedItem
(type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
Identifier
ETD_5295
PhysicalDescription
Form
(authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xiv, 106 p. : ill.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = statement of responsibility)
by Li Gu
Subject
(authority = ETD-LCSH)
Topic
Small interfering RNA
RelatedItem
(type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
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rucore19991600001
Location
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T36Q1V9Z
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
RightsDeclaration
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The author owns the copyright to this work.
RightsHolder
(type = personal)
Name
FamilyName
Gu
GivenName
Li
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = start)
2014-01-05 22:45:09
AssociatedEntity
Name
Li 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.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical
RULTechMD
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ContentModel
ETD
OperatingSystem
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windows xp
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