Supervisors info:
Κωνσταντίνος Δεμέτζος, Καθηγητής, Τμήμα Φαρμακευτικής, ΕΚΠΑ
Χαρπίδου Ανδριανή, Επιστημονική Συνεργάτης, Ιατρική Σχολή ΕΚΠΑ
Γκιόζος Ιωάννης, Ακαδημαϊκός Υπότροφος, Ιατρική Σχολή ΕΚΠΑ
Summary:
Alzheimer's Disease (AD), a progressive neurodegenerative disease, is highly prevalent among the rapidly increasing elderly population in the developing world and is characterized by a gradual decline in cognitive functions. AD is evidenced by the accumulation of extracellular amyloid plaques (Aβ), leading to the degeneration of vulnerable areas of the brain. Current therapeutic approaches primarily involve the administration of drugs via oral, parenteral, and transdermal routes to improve cognitive function and alleviate symptoms, but not to cure the disease. However, these therapies face limitations such as low bioavailability, blood-brain barrier (BBB) permeability constraints, expression of metabolic enzymes, and inadequate penetration. Due to their gastrointestinal side effects and lack of targeting to the brain, these drugs and dosage regimens hinder patient compliance and lead to treatment discontinuation. Alternative invasive methods, while being explored, often entail discomfort and require specialized assistance.
Therefore, the development of a non-invasive and effective delivery system is crucial. Nanotechnology-based drug delivery systems administered through various routes can be considered promising tools to improve patient compliance and achieve better therapeutic outcomes. Nanotechnology has attracted significant scientific interest, offering alternative methods to enhance treatments for AD. These include enhancing drug penetration through the BBB and increasing drug bioavailability via nanoparticle delivery systems, as well as reducing side effects. Additionally, intranasal delivery has emerged as a potential solution, though it is limited by the unique conditions of the nasal cavity. An innovative approach involves the use of nanotechnology-based nanocarriers for intranasal delivery. This strategy has the potential to overcome current limitations by providing enhanced bioavailability, improved penetration, effective BBB crossing, extended retention within the body, and precise targeting of the brain.
This thesis presents current theories regarding the development, pathogenesis, and progression of AD, the contribution of AD models using C. elegans to understanding the mechanisms of the disease, and an analysis of factors influencing neurodegenerative diseases, such as lysosomes and mitochondria. Furthermore, it discusses recent advancements in nanotechnology for the treatment of AD, with a focus on various types of nanodrugs and nanocarriers, including polymer nanoparticles, metal nanoparticles, lipid nanoparticles, liposomes, nanoemulsions, and dendrimers. Special attention is given to the intranasal delivery of nanoparticles for the treatment of Alzheimer's disease, clinical trials, and the prospects of nanotechnology in drug delivery to the brain.
Keywords:
Neurodegenerative Diseases, Alzheimer's Disease (AD), Central Nervous System (CNS), Blood-Brain Barrier (BBB), Lysosomes, Mitochondria, Nanotechnology, Drug Delivery, Targeted Therapy, Nanocarriers, Nanoparticles, Therapeutic Strategies, Intranasal Administration
