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Poly(ethylene glycol) (PEG) nanocarrier-based hydrogels for the prevention of vaginal HIV transmission
Descriptive
TitleInfo
Title
Poly(ethylene glycol) (PEG) nanocarrier-based hydrogels for the prevention of vaginal HIV transmission
Name
(type = personal)
NamePart
(type = family)
Sundara Rajan
NamePart
(type = given)
Sujata
NamePart
(type = date)
1982-
DisplayForm
Sujata Sundara Rajan
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Sinko
NamePart
(type = given)
Patrick J.
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Patrick J. Sinko
Affiliation
Advisory Committee
Role
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chair
Name
(type = personal)
NamePart
(type = family)
Uhrich
NamePart
(type = given)
Kathryn E.
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Kathryn E. Uhrich
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Roth
NamePart
(type = given)
Charles
DisplayForm
Charles Roth
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Chikindas
NamePart
(type = given)
Michael L.
DisplayForm
Michael L. Chikindas
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
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(authority = RULIB)
school
TypeOfResource
Text
Genre
(authority = marcgt)
theses
OriginInfo
DateCreated
(qualifier = exact)
2013
DateOther
(qualifier = exact);
(type = degree)
2013-05
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Women account for over half the global population with HIV. Given the high rate of new infections, the implementation of female-controlled preventive methods is critical to successfully curb HIV. Toward this end, vaginal microbicides- topically applied, self-administered products that protect against HIV are being investigated. A primary risk factor for cervicovaginal HIV acquisition is bacterial vaginosis (BV). BV is characterized by overgrowth of anerobic bacteria and decrease in healthy vaginal lactobacilli and acidity. The compromised vaginal environment in women with BV significantly increases their susceptibility to HIV. Thus a microbicide aimed at preventing and treating BV is likely to be effective at HIV prophylaxis. The overall goal of this thesis is to develop and evaluate poly(ethylene) glycol (PEG) nanocarrier-based hydrogels for application as vaginal microbicides. The hydrogels are formed in situ by covalently cross-linking 8-arm PEG-SH and 4-arm PEG-NHS polymers via degradable thioester bonds. First, the vaginal coverage, distribution and retention of the hydrogels in mice were evaluated using MRI. Hydrogel volumes and surface contact were measured at various times post-dose and compared with hydroxyethylcellulose (HEC) gel. The hydrogels showed significantly longer vaginal retention (12-24 h) than HEC gel (2 h). In the second part of this thesis, PEG nanocarrier-based hydrogels for the controlled release of lactic acid were developed for maintaining vaginal acidity in women with BV. Nanocarrier-based hydrogels with covalently attached lactic acid showed sustained release (10-14% lactic acid) over several days, while hydrogels with passively entrapped lactic acid showed burst release (90% release within 30 min). Hydrogels with passively entrapped lactic acid inhibited the predominant BV pathogen Gardnerella vaginalis. The cytotoxicity of the polymers was also evaluated using vaginal epithelial cells. Finally, hydrogels for the controlled release of subtilosin, an antimicrobial peptide with activity against G. vaginalis was developed. Subtilosin release from the hydrogels was two-phase with initial rapid release (4 µg/hr for 12 h) followed by slow release (0.26 µg/hr from 12-120 h). Subtilosin-containing hydrogels inhibited G. vaginalis but did not significantly inhibit healthy vaginal lactobacilli spp. The antiviral activity of subtilosin against HIV was investigated and subtilosin weakly inhibited HIV replication (IC50= 5.8 µM).
Subject
(authority = RUETD)
Topic
Biomedical Engineering
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
Identifier
ETD_4586
PhysicalDescription
Form
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electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xv, 127 p. : ill.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = statement of responsibility)
by Sujata Sundara Rajan
Subject
(authority = ETD-LCSH)
Topic
HIV infections--Prevention
Subject
(authority = ETD-LCSH)
Topic
Women--Diseases--Prevention
Subject
(authority = ETD-LCSH)
Topic
Colloids in medicine
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000068979
RelatedItem
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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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/T3RN36FX
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
Sundara Rajan
GivenName
Sujata
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
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(qualifier = exact);
(point = start)
2013-04-05 13:48:50
AssociatedEntity
Name
Sujata Sundara Rajan
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
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(qualifier = exact);
(point = start)
2013-05-31
DateTime
(encoding = w3cdtf);
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(point = end)
2015-05-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after May 31st, 2015.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical
RULTechMD
(ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem
(VERSION = 5.1)
windows xp
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