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Study of stimuli-responsive degradation using a disulfide platform in different polymeric biomaterials

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Study of stimuli-responsive degradation using a disulfide platform in different polymeric biomaterials

Aleksanian, Samuel (2014) Study of stimuli-responsive degradation using a disulfide platform in different polymeric biomaterials. Masters thesis, Concordia University.

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Abstract

Polymers have great potential as building blocks to construct biomaterials for applications in biomedicine, pharmaceutics and biotechnology. Their chemical flexibility leads to the synthesis of materials with diverse physical and mechanical properties. Specifically, stimuli-responsive polymers are engineered to undergo chemical or physical transitions in response to specific external triggers. One such response involves the cleavage or degradation of a dynamic covalent bond within the polymer structure. Particularly, the reduction of disulfide bonds has gained significant attention in the development of complex delivery systems for therapeutics. This thesis describes the development of two different reduction-responsive biomaterials.
Amphiphilic block copolymers (ABPs) self-assemble in aqueous solutions to form core/shell micelles consisting of a hydrophobic core, capable of carrying a variety of hydrophobic therapeutic agents, and a hydrophilic corona, able to improve circulation time and delay immune responses. This unique property, in addition to enhanced colloidal stability and tunable size with narrow size distribution, makes micelles promising candidates for drug delivery systems. Hence, a polyester-based reduction-responsive degradable ABP with disulfide linkages positioned repeatedly on the main chain at regular intervals is synthesized. These well-defined ABPs were synthesized by a combination of polycondensation and atom transfer radical polymerization (ATRP). These ABPs self-assemble in aqueous solution, resulting in spherical micelles with a monomodal distribution. In the presence of a reducing agent, disulfide bonds are cleaved, leading to a destabilization of the micellar core and thus enhanced release of encapsulated model drugs. Demonstrating the potential drug delivery applications of polymeric micellar systems, functionalization with biotin (vitamin H) leads to bioconjugated micelles capable of potential cell-targeting.
Hydrogels are three-dimensional networks of hydrophilic polymers that have shown promise as tissue engineering scaffolds. Thermo-responsive hydrogels expel water above their lower critical solution temperature (LCST), becoming more hydrophobic, and hence lose volume. Hydrogels were synthesized by ATRP using biocompatible oligo(ethylene oxide) as a scaffolding material in the presence of a disulfide-labeled dimethacrylate cross-linker. The amount of cross-linker affects thermo-responsive and mechanical properties. Cleavage of disulfide bonds lead to an increased LCST, enhanced deswelling kinetics and a decrease in mechanical properties caused by the generation of hydrophilic dangling chains, increasing the overall hydrophilicity of hydrogels. Combined with these results, as well as enhanced release of encapsulated hydrophilic model drugs and non-toxicity, these hydrogels show promise for biomedical applications.

Divisions:Concordia University > Faculty of Arts and Science > Chemistry and Biochemistry
Item Type:Thesis (Masters)
Authors:Aleksanian, Samuel
Institution:Concordia University
Degree Name:M. Sc.
Program:Chemistry
Date:14 January 2014
Thesis Supervisor(s):Kwon Oh, Jung
ID Code:978343
Deposited By: SAMUEL ALEKSANIAN
Deposited On:30 Jun 2014 20:17
Last Modified:18 Jan 2018 17:46
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