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Development of stimuli-responsive degradable block copolymer micelles as smart drug delivery nanocarriers

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Development of stimuli-responsive degradable block copolymer micelles as smart drug delivery nanocarriers

Khorsand Sourkohi, Behnoush (2013) Development of stimuli-responsive degradable block copolymer micelles as smart drug delivery nanocarriers. Masters thesis, Concordia University.

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Abstract

Polymer-based drug delivery systems offer the potential to increase the bioavailability of drug molecules without leaving toxic byproducts in the body. In particular, micellar aggregates based on amphiphilic block copolymers (ABPs) consisting of a hydrophobic core and a hydrophilic corona can enable the physical encapsulation of poorly water-soluble drugs. These micelles possess several advantages as drug delivery carriers due to their colloidal stability and tunable sizes with narrow size distribution. In addition, their physicochemical properties and small size enable passive tumor targeting through the enhanced permeability and retention effect. Also their chemical flexibility allows them to be tailored for active targeting. One additional benefit of using ABP-based micelles is that they can be engineered to incorporate stimuli-responsive moieties to control release of encapsulated drugs as a result of micellar degradation in response to external triggers such as pH, thiols and temperature. With this knowledge, ABP micelles can be designed with the ability to respond to stimuli that are inherently present in living systems and release their payload before being evacuated from the body. Presence of pH and redox gradients within the body makes them ideal stimuli in the design and development of stimuli-responsive degradable micelles for controlled release of therapeutics.
For better understanding of the structure-property relationship between morphological variance and stimuli-responsive degradation, we have developed new pH-sensitive degradable micelles having pendant t-butyl groups, as well as reductively degradable ABP micelles with single disulfide linkages positioned in the center of triblock copolymers, or with pendant disulfides positioned on the hydrophobic block. They were synthesized by atom transfer radical polymerization, a dynamic controlled radical polymerization method enabling the synthesis of copolymers with narrow molecular weight distributions and pre-determined molecular weights. Aqueous self-assembly of ABPs resulted in colloidally stable spherical micelles capable of encapsulating hydrophobic model drugs at above critical micellar concentration. Various analytical methods were used to characterize ABPs and their micelles. The resulting micelles in aqueous solutions were destabilized in response to acidic conditions or reductive conditions, which suggests the possibility of enhanced release of encapsulated compounds. Results show that degradable ABPs of varying architectures and designs, upon the proper stimuli, will be dissociated at different rates, leading to a wide range of morphologies and sustained release rates of the encapsulated molecules.

Divisions:Concordia University > Faculty of Arts and Science > Chemistry and Biochemistry
Item Type:Thesis (Masters)
Authors:Khorsand Sourkohi, Behnoush
Institution:Concordia University
Degree Name:M. Sc.
Program:Chemistry
Date:23 July 2013
Thesis Supervisor(s):Oh, Jung Kwon (John)
Keywords:stimuli-responsive,Block Copolymer, Micelles, Drug Delivery
ID Code:977485
Deposited By: BEHNOUSH KHORSAND SOURKOHI
Deposited On:26 Nov 2013 17:14
Last Modified:18 Jan 2018 17:44
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