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Synthesis and evaluation of novel amphiphilic macromolecules as drug carriers and therapeutics

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Title
Synthesis and evaluation of novel amphiphilic macromolecules as drug carriers and therapeutics
Name (ID = NAME001); (type = personal)
NamePart (type = family)
Wang
NamePart (type = given)
Jinzhong
NamePart (type = date)
1979-
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Jinzhong Wang
Role
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author
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Uhrich
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Kathryn
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Advisory Committee
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Kathryn E Uhrich
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chair
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Castner
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Edward
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Advisory Committee
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Edward Castner
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RoleTerm (authority = RULIB)
internal member
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NamePart (type = family)
Warmuth
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Ralf
Affiliation
Advisory Committee
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Ralf Warmuth
Role
RoleTerm (authority = RULIB)
internal member
Name (ID = NAME005); (type = personal)
NamePart (type = family)
Moghe
NamePart (type = given)
Prabhas
Affiliation
Advisory Committee
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Prabhas V Moghe
Role
RoleTerm (authority = RULIB)
outside member
Name (ID = NAME006); (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (ID = NAME007); (type = corporate)
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Graduate School - New Brunswick
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school
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Text
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theses
OriginInfo
DateCreated (qualifier = exact)
2007
DateOther (qualifier = exact); (type = degree)
2007
Language
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English
PhysicalDescription
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electronic
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application/pdf
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text/xml
Extent
xiv, 121 pages
Abstract
Novel amphiphilic star-like macromolecules (ASM) and amphiphilic scorpion-like macromolecules (AScM) with double-chained and single-chained tails were synthesized and characterized. All macromolecules are composed of mucic acid-based hydrophobic “heads” and poly(ethylene glycol)-based hydrophilic “tails”. Two different ASMs (M12P5 and M12P2x2) and two different AScMs (NC12P5 and NC12P2x2) were investigated to explore how branched PEG chains influence particle size, water-solubility, drug loading capacity, drug release rate and micelle stability. A hydrophobic, anti-inflammatory drug (indomethacin) was used to evaluate the encapsulation ability and release rate from the macromolecules. The double-chained macromolecules reduced the micellar sizes (10 nm for AScM, 22 nm for ASM) compared to single-chained macromolecules (18 nm for AScM, 48 nm for ASM). Through oil/water emulsion methods, drug-loading efficiency of ASM reached nearly 50%, higher than the self-assembled micelle AScMs, which display a drug-loading efficiency 30%. Indomethacin-
loaded ASM released 52% of free drug within 50 hours, compared with 78% for AScM. Dynamic light scattering experiments showed that ASM minimized protein interactions. Double-chained macromolecules perform as well or better than single-chained ones as drug delivery systems.
Several AScMs, which bear carboxylate groups on hydrophilic and hydrophobic domains, were also prepared. These macromolecules formed extremely stable micelles in aqueous solution with an average size of 20-35 nm and critical micelle concentration (CMC) as low as 10-7 M. Zeta potential values and micellar sizes in neutral buffer solutions correlated well with the carboxylate location and numbers. All macromolecules are capable of inhibiting unregulated uptake of highly-oxidized low density lipoproteins (LDL) by macrophages. This inhibition is caused by the interaction of scavenger receptors with negatively charged macromolecules, and closely responds to the number and location of negative charges. The AScM with one carboxylate at the hydrophobic domain and one carboxylate at hydrophilic domain exhibited the best LDL inhibition. To further enhance the treatment, a ligand GW 3965 was loaded into the AScM micelle.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references.
Subject (ID = SUBJ1); (authority = RUETD)
Topic
Chemistry and Chemical Biology
Subject (ID = SUBJ2); (authority = ETD-LCSH)
Topic
Drug delivery systems
Subject (ID = SUBJ3); (authority = ETD-LCSH)
Topic
Drug carriers (Pharmacy)
Subject (ID = SUBJ4); (authority = ETD-LCSH)
Topic
Pharmaceutical technology
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Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.16792
Identifier
ETD_523
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/T3V988H1
Genre (authority = ExL-Esploro)
ETD doctoral
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The author owns the copyright to this work.
Copyright
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Open
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Name
Jinzhong Wang
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
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Type
Permission or license
Detail
Non-exclusive ETD license
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Author Agreement License
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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.
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