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Development of Imine-based pH-responsive Polymeric Drug Delivery Systems


Development of Imine-based pH-responsive Polymeric Drug Delivery Systems

Hu, Xiaolei (2021) Development of Imine-based pH-responsive Polymeric Drug Delivery Systems. Masters thesis, Concordia University.

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Block copolymer-based nanoassemblies that can disassemble in response to endogenous stimuli found in tumor tissues and cancer cells are promising candidates for intracellular drug delivery exhibiting enhanced release of encapsulated drugs. Owning to excellent colloidal stability during blood circulation (pH = 7.4) and accelerated drug release ability in tumoral and endo/lysosomal acidic environments (pH = 4.0-6.8), acid-responsive degradable nanoassemblies have emerged as promising nanocarriers for advanced drug delivery with precisely controlled drug release. Benzoic imine bond, which is cleavable at acidic pH while stable under physiological pH, has been widely explored for the design of novel acid-degradable block copolymers. A general method to synthesize imine-containing block copolymers involves the post-polymerization modification. Functional copolymer precursors bearing primary amine or carbonyl groups are conjugated with hydrophobic moieties, drug molecules, and hydrophilic species through in situ imine formation reaction.
My master research explores a new approach to synthesize acid-degradable block copolymers bearing pendant imine groups (ImPs). The approach explores direct polymerization of a novel imine-containing methacrylate utilizing controlled radical polymerization techniques, enabling the synthesis of well-controlled ImPs with tunable functionalities. The resultant ImPs undergo self-assembly to form nanometer-sized micelles, composed of hydrophilic poly(ethylene glycol) (PEG) corona and acid-degradable hydrophobic core bearing imine linkages. In response to tumoral and endo/lysosomal acidic environments, they disassemble through a change in hydrophilic/hydrophobic balance upon the cleavage of imine linkages to the corresponding aldehyde and primary amine. As a consequence, such acid-catalyzed hydrolysis of imine linkages in hydrophobic cores leads to the enhanced release of encapsulated doxorubicin (Dox, a clinically used anticancer drug).
The proof-of-concept results suggest that this robust approach is versatile to further design advanced nanoassemblies responding to dual/multiple stimuli, thus being more effective to intracellular drug delivery.

Divisions:Concordia University > Faculty of Arts and Science > Chemistry and Biochemistry
Item Type:Thesis (Masters)
Authors:Hu, Xiaolei
Institution:Concordia University
Degree Name:M. Sc.
Date:14 June 2021
Thesis Supervisor(s):Oh, Jung Kwon
ID Code:988592
Deposited By: Xiaolei Hu
Deposited On:29 Nov 2021 16:51
Last Modified:01 Aug 2023 00:00
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