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Identifier |
000443891 |
Title |
Photo- and acid-degradable polyacylhydrazone–doxorubicin conjugates for controlled anticancer drug delivery |
Alternative Title |
Σύνθεση και χαρακτηρισμός συζευγμένων πολυακυλο-υδραζονών - δοξορουβικίνης, διασπώμενων με φως και pH για την ελεγχόμενη απελευθέρωση αντικαρκινικών φαρμάκων |
Author
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Κοθρή, Μάρθα Γεωργία
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Thesis advisor
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Προυσής, Κυριάκος
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Reviewer
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Βαμβακάκη, Μαρία
Καλογεροπούλου, Θεοδώρα
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Abstract |
Cancer is the second leading cause of death worldwide for both men and women and attacks
even the very young ages. In the recent years, significant progress has been made on the
development of pharmaceuticals for the treatment of cancerous tumors. However, the significant
side effects of their conventional route of administration, i.e., the non-selective and uncontrolled
delivery to cancer tissues, have driven the need for controlled drug delivery systems. Drug
delivery systems can safely deliver a drug substance by combining a suitable material with
bioactive molecules or drugs that would otherwise have inadequate activity or undesirable
pharmacokinetic characteristics or would be toxic to healthy normal cells. Polymeric drug delivery
systems that have been investigated range from polymeric micelles, vesicles, hydrogels, etc. The
aim of this thesis is to report the synthesis and characterization of a new, linear, main-chain photoand acid-degradable copolymer based on acylhydrazone linkages. The polymer synthesis was
carried out by the step-growth copolymerization of adipic acid dihydrazide with a bifunctional poly
(ethylene glycol) bearing benzaldehyde end-groups, under mild acidic conditions, to afford
hydrophilic PEG-alt-adipic acid (PEG-alt-AA) alternating copolymers. The synthesized polymers
were characterized by size exclusion chromatography, proton nuclear magnetic resonance and
attenuated total reflection-Fourier transform infrared spectroscopies. The main-chain photo- and
acid-induced degradation of the copolymers in dimethylsulfoxide and water, respectively, to
produce the two precursor comonomers, was verified by UV-vis spectroscopy at light intensities
as low as 0.1 mW cm−2 at λ = 254 nm. Next, a model anticancer drug, doxorubicin (DOX), was
chemically linked to the polymer chain end(s) via acylhydrazone bond(s), resulting in amphiphilic
PEG-alt-adipic acid-DOX (PEG-alt-AA-DOX) polymer–drug conjugates. The conjugates were
self-assembled in water to form spherical nanoparticles, as evidenced by scanning and
transmission electron microscopies and dynamic light scattering. The irradiation of the selfassembled PEG-alt-AA-DOX conjugates with UV light and the simultaneous decrease of the
solution pH resulted in the disruption of the assemblies, due to the combined photolysis and
acidolysis of the acylhydrazone bonds, and led to the controlled release of the therapeutic cargo.
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Language |
English |
Subject |
Polymer -drug conjugates |
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Πολυμερή που διασπώνται με φως και PH |
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Συζευγμένα συστήματα πολυμερών -φαρμάκων |
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Συστήματα μεταφοράς φαρμάκων |
Issue date |
2021-12-01 |
Collection
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School/Department--School of Medicine--Department of Medicine--Post-graduate theses
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Type of Work--Post-graduate theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/b/d/6/metadata-dlib-1640004925-918381-28262.tkl
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Views |
234 |