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Identifier

000419562

Title

Mechanically-induced main chain scission of polyacetals for controlled drug release

Alternative Title

Μηχανικά επαγόμενη διάσπαση της κύριας αλυσίδας πολυακετάλων για ελεγχόμενη αποδέσμευση φαρμάκων

Author

Ψαρρού, Μαρία Χ.

Thesis advisor

Αναστασιάδης, Σπύρος

Reviewer

Βαμβακάκη, Μαρία
Μπαριτάκη, Σταυρούλα

Abstract

Stimuli-controlled drug delivery has attracted enormous attention over the past decades. Several type of nanosized carriers including organic nanoparticles, inorganic nanomaterials or combinations of organic/inorganic materials have been extensively studied for the controlled delivery of active compounds at specific areas such as tumor tissues. The stimuli that trigger drug release from the nanocarriers can be broadly classified in two main classes: the internal stimuli such as pH, glutathione and enzymes and the external stimuli (physical stimuli) such as light irradiation, magnetic and electric fields and ultrasound. Ultrasound in particular is one of the most promising external triggers for controlled drug release from polymeric nanocarriers because it offers great spatiotemporal control, deep tissue penetration (deeper than light irradiation) and is a non-invasive and non-ionizing method. Smart materials in the form of stimuli-responsive amphiphilic block copolymers are of great interest and have been widely used for the development of responsive drug nanocarriers. They can self-assembled into core-shell micelles in aqueous solution and can solubilize hydrophobic molecules (e.g. drugs) into their hydrophobic core. Herein, we present a new class of dual, ultrasound and pH, degradable drug carriers based on PEG-b-polyacetal block copolymers. For this study, the homopolymer polyacetals and the PEG-b-polyacetal copolymers were synthesized using a facile and scalable chemistries without incorporation of toxic reagents. An extensive sono-degradation study of the polyacetal homopolymers using both low and high frequency ultrasound verified the main-chain degradation of the polyacetals due to the generation of elongation flows from cavitation setting the acetal bond a very “weak” mechano-labile group. Also, sono-degradation experiments in organic media proved the main-chain degradation of the PEG-b-polyacetal block copolymers into low molecular weight products. Next, the block copolymers were self-assembled into spherical micelles in water and Sudan Red was used as a model payload, to examine the release behavior of the micelles under different sonication conditions. The results showed that our system can be degraded into small hydrophilic and non-toxic molecules while releasing its cargo in the surrounding medium using medical ultrasound at 1 MHz frequency and extremely low irradiation energies. Moreover, the combination of low solution pH and ultrasound irradiation increased the release efficiency from the carriers suggesting, a particularly effective combinatorial dual stimuli induced release.

Language

English

Subject

Controlled drug delivery

Drug release

Polyacetols

Ultrasount

Αποδέσμευση φαρμάκων

Ελεγχόμενη μεταφορά

Πολυακετάλες

Υπέρηχοι

Issue date