Modification of Alginate and Development of Polymeric Nanocarriers by Living Radical Polymerization for Controlled/Targeted Drug Delivery
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Authors
Kapishon, Vitaliy
Date
2015-12-03
Type
thesis
Language
eng
Keyword
Living Radical Polymerization , Drug Delivery , Alginate , Biomaterials
Alternative Title
Abstract
Alginate-based amphiphilic graft copolymers were synthesized by single electron transfer living radical polymerization (SET-LRP), forming stable micelles during polymerization induced self-assembly (PISA). First, alginate macroinitiator was prepared by partial depolymerization of native alginate, solubility modification and attachment of initiator. Then, methyl methacrylate was polymerized from the alginate macroinitiator in mixtures of water and methanol forming poly(methyl methacrylate) grafts, prior to self-assembly. PISA of the amphiphilic graft-copolymer resulted in the formation of micelles with diameters of 50-300 nm. As the first reported case of LRP from alginate, this work introduces a synthetic route to of alginate-based hybrid polymers with a precise macromolecular architecture and desired functionalities. LRP from alginate can be applied to improve alginate-based hydrogel systems such as nano- and micro-hydrogel particles, islet encapsulation materials, hydrogel implants and topical applications. Such modified alginates can also improve the function and application of native alginates in food and agricultural technologies.
Targeted drug delivery using polymeric nanostructures has been at the forefront of cancer research engineered for safer, more efficient and effective use of chemotherapy. Here, a new polymeric micelle delivery system was designed for active tumor targeting via receptor-induced endocytosis. Oseltamivir phosphate targets and inhibits Neu1 sialidase activity associated with receptor tyrosine kinases such as epidermal growth factor (EGF) receptors which are overexpressed on cancer cells. By decorating micelles with oseltamivir, it was found that micelles actively targeted human pancreatic PANC1 cancer cells. Amphiphilic block copolymers with oseltamivir conjugated at the hydrophilic end, oseltamivir-poly(polyethylene glycol methyl ether methacrylate)-block-poly(methyl methacrylate), were synthesized using reversible addition-fragmentation chain transfer (RAFT) living radical polymerization. Oseltamivir-conjugated micelles have self-assembling properties forming worm-like micellar structures. Oseltamivir-conjugated micelles dose dependently reduced the cell viability of PANC1 cells compared to micelles without oseltamivir. Oseltamivir-micelles loaded with hydrophobic dye produced internalization by PANC1. These results clearly indicate that oseltamivir-conjugated micelles show potential as an entirely new active tumor targeting drug delivery system with the ability to internalize hydrophobic chemotherapeutics by receptor-mediated endocytosis.
Description
Thesis (Ph.D, Chemical Engineering) -- Queen's University, 2015-12-01 14:50:52.955
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This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
Creative Commons - Attribution - CC BY
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.