RUcore: Rutgers University Community Repository
Design of poly (alkylene oxide) graft copolymer chemistries for improved antisense drug delivery
Descriptive
TitleInfo
Title
Design of poly (alkylene oxide) graft copolymer chemistries for improved antisense drug delivery
Name
(type = personal)
NamePart
(type = family)
Peddada
NamePart
(type = given)
Lavanya Y.
NamePart
(type = date)
1983-
DisplayForm
Lavanya Peddada
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Roth
NamePart
(type = given)
Charles M
DisplayForm
Charles M Roth
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
chair
Name
(type = personal)
NamePart
(type = family)
Devore
NamePart
(type = given)
David I
DisplayForm
David I Devore
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Moghe
NamePart
(type = given)
Prabhas V
DisplayForm
Prabhas V Moghe
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Cai
NamePart
(type = given)
Li
DisplayForm
Li Cai
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Minko
NamePart
(type = given)
Tamara
DisplayForm
Tamara Minko
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
(qualifier = exact)
2012
DateOther
(qualifier = exact);
(type = degree)
2012-01
CopyrightDate
(qualifier = exact)
2012
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Gene-based therapies hold tremendous promise to treat conditions such as cancer, muscular dystrophy, and cardiovascular disease. Non-viral carriers consisting of synthetic and natural cationic polymers, liposomes, and non-ionic copolymer micelles have demonstrated moderate success in overcoming some of the delivery challenges. At the systemic level, the issues of drug degradation in the bloodstream and poor pharmacological distribution to target disease site exist. At the cellular level, the key barrier involves escape of the carrier and therapeutic cargo from the degradative endolysosomal pathway. Efforts have been made to understand and to design carrier chemistries based on physical properties including particle size, particle surface charge, degree of carrier hydrophilicity/hydrophobicity, polymer conformation, etc. To date, clear design rules based on physicochemical properties have not emerged. Previously, our group has formulated a multi-component liposome-based carrier system that efficiently delivers antisense oligonucleotide in the absence of serum, but which is considerably less active in the presence of serum. This motivated us to improve the existing carrier chemistry for improved delivery in the presence of extracellular nucleases and serum proteins, while maintaining the function of evading intracellular barriers. In this dissertation, we provide a comprehensive evaluation of graft copolymers consisting of poly (propylacrylic acid) and poly (alkylene oxide) chemistries with varying degrees of hydrophobicity to hydrophilicity, and describe the influence of this parameter on liposome-mediated antisense gene delivery. First, various steps involved in the antisense gene delivery process including serum-stability, membrane penetration, and endosome membrane lysis was evaluated in vitro. Secondly, we address the hypothesis that liposomes stabilized with poly (alkylene oxide) graft copolymers can improve biodistribution by using a tumor xenograft model that allows us to relate biodistribution profiles to nanoparticle size, surface charge, and polymer architecture. Our findings indicate that the balance of polymer hydrophobicity to hydrophilicity plays a key role in dictating serum-stability and cellular entry in vitro, as well as fate of antisense in vivo.
Subject
(authority = RUETD)
Topic
Biomedical Engineering
RelatedItem
(type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
Identifier
ETD_3802
PhysicalDescription
Form
(authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xvi, 100 p. : ill.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = vita)
Includes vita
Note
(type = statement of responsibility)
by Lavanya Y. Peddada
Subject
(authority = ETD-LCSH)
Topic
Drug delivery systems
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000064160
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/T3FQ9VNN
Genre
(authority = ExL-Esploro)
ETD doctoral
Back to the top
Rights
RightsDeclaration
(ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder
(type = personal)
Name
FamilyName
Peddada
GivenName
Lavanya
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = start)
2012-01-06 14:56:32
AssociatedEntity
Name
Lavanya Peddada
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)
2012-01-31
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = end)
2012-08-01
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after August 1st, 2012.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
Back to the top
Technical
FileSize
(UNIT = bytes)
1566720
Checksum
(METHOD = SHA1)
7cd8738babfcf95e315a27921517d00071c0e69b
OperatingSystem
(VERSION = 5.1)
windows xp
ContentModel
ETD
MimeType
(TYPE = file)
application/pdf
Back to the top
Statistical Profile