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Engineering polymeric matrices for c...

Liang, Yingkai.

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Engineering polymeric matrices for controlled drug delivery applications: From bulk gels to nanogels.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Engineering polymeric matrices for controlled drug delivery applications: From bulk gels to nanogels./
Author:	Liang, Yingkai.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2016,
Description:	193 p.
Notes:	Source: Dissertation Abstracts International, Volume: 78-04(E), Section: B.
Contained By:	Dissertation Abstracts International78-04B(E).
Subject:	Materials science. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10192030
ISBN:	9781369351644

Engineering polymeric matrices for controlled drug delivery applications: From bulk gels to nanogels.
Liang, Yingkai.

Engineering polymeric matrices for controlled drug delivery applications: From bulk gels to nanogels. - Ann Arbor : ProQuest Dissertations & Theses, 2016 - 193 p.

Source: Dissertation Abstracts International, Volume: 78-04(E), Section: B.

Thesis (Ph.D.)--University of Delaware, 2016.

In this work, we have specifically engineered polyethylene glycol (PEG) hydrogel matrices from bulk to nanoscale, including bulk hydrogels, nanoparticle-crosslinked hybrid hydrogels and nanogels for different delivery applications. Firstly, a library of hydrophilic and hydrolytically degradable PEG hydrogels has been developed for the sustained delivery of an anthrax toxin-neutralizing monoclonal antibody from 14--56 days. The hydrogels were formed via a Michael-type addition between multi-arm PEG-SH and hydrolytically degradable crosslinkers of linear PEG-diacrylate. By varying the polymer architectures and molecular weights of the precursors, the degradation rate of the matrix can be systematically tuned, which in turn tailors the rate of antibody release from the hydrogels. In-gel and post-release analysis of the antibody samples indicate that the conformational properties and biological activity of the protein were well maintained.

ISBN: 9781369351644Subjects--Topical Terms:

543314
Materials science.

Engineering polymeric matrices for controlled drug delivery applications: From bulk gels to nanogels.
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500 $a Source: Dissertation Abstracts International, Volume: 78-04(E), Section: B.
500 $a Adviser: Kristi L. Kiick.
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520 $a In this work, we have specifically engineered polyethylene glycol (PEG) hydrogel matrices from bulk to nanoscale, including bulk hydrogels, nanoparticle-crosslinked hybrid hydrogels and nanogels for different delivery applications. Firstly, a library of hydrophilic and hydrolytically degradable PEG hydrogels has been developed for the sustained delivery of an anthrax toxin-neutralizing monoclonal antibody from 14--56 days. The hydrogels were formed via a Michael-type addition between multi-arm PEG-SH and hydrolytically degradable crosslinkers of linear PEG-diacrylate. By varying the polymer architectures and molecular weights of the precursors, the degradation rate of the matrix can be systematically tuned, which in turn tailors the rate of antibody release from the hydrogels. In-gel and post-release analysis of the antibody samples indicate that the conformational properties and biological activity of the protein were well maintained.
520 $a In addition to bulk hydrogels for the long-term delivery of therapeutics, stimuli-responsive, nanoparticle-crosslinked hybrid hydrogels have also been introduced for the triggered and targeted release of therapeutic molecules. These hybrid hydrogels were constructed using maleimide-functionalized liposomes (~100nm) as structural elements to crosslink with thiolated 4-arm PEG polymers via Michael-type addition. Degradation of these hydrogels was selectively triggered upon exposure to thiol-containing molecules such as glutathione (GSH), offering great advantages for controlled and triggered release of therapeutic cargos under reducing environments that are analogous to the GSH-overproduced tumor microenvironment. The hierarchical structure of these hybrid hydrogels allows dual encapsulation and prolonged, sequential delivery of multiple therapeutic molecules with different release mechanism.
520 $a Motivated by the significant impact of nanotechnology on the development of nanoscale drug delivery vehicles, PEG nanogels that combine the advantages of both nanoparticulate and polymeric hydrogel systems were prepared via the use of liposome templates. The nanogels were formed by photo-triggered Michael-type addition of PEG polymer precursors encapsulated within the aqeuous lumen of liposomes under UV irradiation. The production of nanogels was confirmed via dynamic light scattering (DLS) and transmission electron microscopy (TEM). The surface functionality of the lipid-coated nanogels was demonstrated by surface modification with a reactive fluorescent dye as a proof of concept.
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