Unit:
Department of PharmacyLibrary of the School of Science
Dissertation committee:
Κωνσταντίνος Δεμέτζος, Καθηγητής, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)
Αστέριος Πίσπας, Διευθυντής Ερευνών, Ινστιτούτο Θεωρητικής και Φυσικής Χημείας, Εθνικό Ίδρυμα Ερευνών
Κωνσταντίνος Δήμας, Αναπληρωτής Καθηγητής, Τμήμα Ιατρικής, Πανεπιστήμιο Θεσσαλίας
Ερμής Ιατρού, Καθηγητής, Τμήμα Χημείας, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)
Νικόλαος Δρακούλης, Αναπληρωτής Καθηγητής, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)
Μαριλένα Βλάχου, Επίκουρη Καθηγήτρια, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)
Maria Bryszewska, Professor, Faculty of Biology and Environmental Protection, University of Lodz
Original Title:
Design, Technological Development and Evaluation of Stimuli-responsive Chimeric Nanocarriers for Cancer Therapy
Translated title:
Design, Technological Development and Evaluation of Stimuli-responsive Chimeric Nanocarriers for Cancer Therapy
Summary:
Nanotechnology has achieved great breakthroughs in our era, with applications that exceed the capabilities of conventional strategies in many scientific fields, including Medicine and Pharmacy. Nanomedicine has thrived since the development of the first nanotechnological products in the late 20th century and has evolved to be one of the most promising endeavors in fighting human diseases. In this context, liposomes have long been utilized as nanotechnological carriers of drug molecules and are considered one of the most well-known platforms for this purpose. These cell-like nanocarriers exhibit structure and properties in the mesoscale that are dynamic, governed by the mechanism and laws of self-assembly. This process is of critical importance for the development of new innovative nanomedicinal products, as well as for the regulation of their follow-up “nanosimilar” products.
The present PhD thesis deals with the modern issue of stimuli-responsive chimeric/mixed nanocarriers for cancer therapy, which belong to the class of advanced drug delivery nanosystems (aDDnSs) for complex diseases. Aim of the research was to rationaly design and develop chimeric nanosystems that respond to certain physical and physiological conditions, i.e. temperature alterations and pH variations, as well as to evaluate their self-assembly, final properties and in vitro and in vivo behavior. These nanosystems are comprised of two different classes of biomaterials, namely phospholipids and amphiphilic diblock copolymers and are promising candidates for cancer therapy, by delivering and releasing therapeutic agents selectively to the disease site.
The analytical tools utilized for the evaluation of the biomaterial interactions and their self-assembly contribute to the development of quality nanotechnological formulations, by offering insight into the nanoscale properties of such systems and their connection with the final nanocarrier. These tools are associated with the thermodynamics, physicochemical properties, stability, morphology, biophysics and functionality and finally, with the biological toxicity and effectiveness of chimeric nanosystems. In particular, they included thermal analysis, such as differential scanning calorimetry (DSC) or micro-DSC, fluorescence spectroscopy, light scattering, imaging techniques, like transmission electron microscopy (TEM) and cryo-TEM and ultimately, biological assays, through in vitro and in vivo models. By obtaining the full profile of a nanosystem, such as liposomes, based on these tools, not only we may develop innovative drug delivery nanoplatforms, but we may also understand the role of the individual molecules, e.g. lipids and polymers, and of the self-assembly process in the final medicinal product.
Ultimately, the present PhD work led to the development of biocompatible and functional chimeric nanosystems, which are promising as drug delivery platforms in cancer therapy, through their stimuli-responsive behavior. The importance of establishing a rationale of evaluation for these nanosystems through the integration of certain important tools is also conspicuous and may provide knowledge for further development of innovative medicines. Additionally, they may contribute to the study and authorization of their follow-up products, known as “nanosimilars”. These tools regard the evaluation of the self-assembly mechanism and its relationship with the final properties, toxicity and functionality of aDDnsS, aiding the production of quality, safe and effective innovative nanomedicines for cancer therapy.
Main subject category:
Health Sciences
Keywords:
Nanocarriers, Chimeric, Stimuli-responsive, Liposomes, Self-assembly, Thermodynamics, DSC, Biophysics, Morphology, TEM, Toxicity, Tram-34
Number of references:
273
