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Investigation of biodegradable poly(anhydride-esters) hydrolysis through in vitro modeling and kinetic analyses

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TitleInfo
Title
Investigation of biodegradable poly(anhydride-esters) hydrolysis through in vitro modeling and kinetic analyses
Name (type = personal)
NamePart (type = family)
Bien-Aime
NamePart (type = given)
Stephan
NamePart (type = date)
1990-
DisplayForm
Stephan Bien-Aime
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Uhrich
NamePart (type = given)
Kathryn E
DisplayForm
Kathryn E Uhrich
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Romsted
NamePart (type = given)
Larry S
DisplayForm
Larry S Romsted
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Warmuth
NamePart (type = given)
Ralf
DisplayForm
Ralf Warmuth
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal 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)
2015-10
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2015
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Chemical incorporation of bioactives into polymers allows for their controlled and sustained delivery. Poly(anhydride-esters) (PAEs) are predominantly surface-eroding polymers, providing sustained release of bioactives. Compared to physical formulations, PAEs are capable of achieving higher bioactive loading (50 – 80 %) and have the versatility of being formulated into different geometries (discs, films), hence offering the potential to satisfy diverse administration routes in drug delivery. In this thesis, biodegradable polymers that contain salicylic acid and pinosylvin as bioactives within PAEs are employed, and their hydrolysis investigated. In one approach, a novel agar-based in vitro model mimicking the in vivo environment of the mandibular bone defect in diabetic animals was developed. Localized and systemic release profiles of salicylic acid from salicylic acid-based PAEs were evaluated. A sustained localized SA release was observed for 70 days. This study shows the agar-based system is a preferred model to mimic the in vivo mandibular bone defect environment, and may be an appropriate method to mimic in vivo pharmacokinetics of other drugs in related animal models. In another approach, pinosylvin was chemically incorporated into a PAE backbone via melt-condensation polymerization, and fully characterized with respect to its physicochemical and thermal properties. In vitro release studies in phosphate buffered saline (pH 7.4) demonstrated that pinosylvin-based polymers underwent slow hydrolytic degradation. Pseudo-first order kinetic experiments on butyric anhydride and 3-butylstilbene ester model compounds showed the anhydride underwent faster hydrolysis [k = (30.6 ± 2.24) × 10-6 L mol-1 s-1] than the ester [k = (56.7 ± 5.01) × 10-7 L mol-1 s-1)]. These results suggest that in solution, the anhydride linkages of pinosylvin PAEs are more labile and hydrolyzed first, followed by hydrolytic cleavage of the ester bonds to release pinosylvin. A disc diffusion antibacterial assay showed polymer release media exhibited similar bioactivity as free pinosylvin. In vitro cytocompatibility studies demonstrated that the polymer was non-cytotoxic towards fibroblasts up to 0.5 μg/mL. Based upon the results, pinosylvin-based polymers are slowly degradable biomaterials that provide antibacterial activity, and thus can serve as food additives into common food packaging materials for food preservation and food safety.
Subject (authority = RUETD)
Topic
Chemistry and Chemical Biology
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_6845
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xiii, 42 p. : ill.)
Note (type = degree)
M.S.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = ETD-LCSH)
Topic
Drug delivery systems
Subject (authority = ETD-LCSH)
Topic
Anhydrides
Note (type = statement of responsibility)
by Stephan Bien-Aime
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/T3930W5X
Genre (authority = ExL-Esploro)
ETD graduate
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Bien-Aime
GivenName
Stephan
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2015-09-30 18:16:42
AssociatedEntity
Name
Stephan Bien-Aime
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 (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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