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Identifier 000416058
Title Αυτοθυσιαζόμενα μεταλλο-διφωσφονικά πολυμερή συναρμογής ως συστήματα ελεγχόμενης αποδέσμευσης του διφωσφονικού αντιοστεοπορωτικού φαρμάκου
Alternative Title Self-sacrificial metal-bisphosphonate coordination polymers as controlled delivery systems of the antiosteoprotic drug
Author Βασσάκη, Μαρία Μ.
Thesis advisor Δημάδης, Κωνσταντίνος
Reviewer Μήλιος, Κωνσταντίνος
Τρικαλίτης, Παντελεήμων
Abstract The combination of metal ions and bisphosphonic acids (BPs) yields metal phosphonate hybrid materials. The majority of these metal phosphonates are coordination polymers where metal ions are connected with BP linkers, thus creating a variety of structural motifs (1D, 2D, or 3D, and less frequently 0D), depending on the idiosyncrasies of the metal center and the BP. In this work we present new biocompatible metal phosphonate materials have been synthesized by combining either “first-generation” (non-nitrogen BPs), and “second-generation” (nitrogen-containing, N-BPs), and biocompatible alkaline-earth metal ions (eg. Mg2+, Ca2+, Sr2+ and Ba2+). The synthesized products are, essentially, metal-drug complexes and “coordination polymers“, in which the linker (BP) that connects the metal nodes is an active pharmaceutical ingredient. The aforementioned BPs constitute a class of drugs against osteoporosis and other bone-related diseases. The P-C-P moiety is responsible for the strong affinity of BPs for binding to hydroxyapatite (HAP) present in bone. Their success in mitigating osteoporosis notwithstanding, these BP drugs present a number of challenges including limited bioavailability, fast excretion, and numerous side-effects, such as osteonecrosis of the jaw, hypocalcemia, esophageal cancer, ocular inflammation, atrial fibrillation, etc. It is, therefore, imperative to design and fabricate “smart” systems that allow controlled delivery of the active BP agent, which will depend on the patient’s needs and idiosyncrasies. In the present work, these metal-drug hybrid materials were evaluated for their ability to release the active BP in a predictable and controlled manner. This controlled release is achieved through low pH-driven degradation of the metal-drug framework under specific biological conditions that mimic the human stomach. The drug release was quantified by 1Η NMR spectroscopy. The results are visualized in diagrams containing release curves correlating % drug release vs. time. Lastly, structure-activity relationships are attempted, in an effort to correlate structure with drug release efficiency.
Language Greek
Subject Biocompatible
Bisphosphonates
Controlled drug release
Metal-drug hybrid materials
Osteoporosis
Βιοσυμβατά
Διφωσφονικοί υποκαταστάτες
Ελεγχόμενη αποδέσμευση φαρμάκου
Μεταλλοφωσφονικά υβριδικά υλικά
Οστεοπόρωση
Issue date 2018-07-18
Collection   School/Department--School of Sciences and Engineering--Department of Chemistry--Post-graduate theses
  Type of Work--Post-graduate theses
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