Nörodejeneratif Hastalıklara Yönelik Memantin Yüklü Nanosistemlerin Tasarlanması, Optimizasyonu ve Değerlendirilmesi

Abstract

Tezel, G., Design, Optimization and Evaluation of Nanosystems Loaded with Memantine for Neurodegenerative Diseases, Hacettepe University Graduate School of Health Sciences Pharmaceutical Technology Doctor of Philosophy Thesis, Ankara, 2024. Alzheimer's Disease (AD), a neurodegenerative disorder of the central nervous system, is highlighted as a disease with a high medical need due to both its frequency and the inability to effectively treat it yet, largely due to limiting factors. Within the scope of thesis studies, in an effort to address the unmet medical need in the treatment of AD, memantine-loaded nanomotor systems have been designed for the first time. Within this framework, the design of nanomotor formulations containing memantine, the investigation of the effectiveness of these formulations in neuronal cell culture models in vitro, the examination and documentation of these nanosystems on metabolic changes encountered in AD in vitro cell culture models, and finally the evaluation of the accumulation of these nanosystems in the Blood-Brain Barrier (BBB) and brain tissue using appropriate techniques have been conducted, and the results have been evaluated. As a result, memantine loaded nanomotors were formulated successfully with a controllable magnetic movement. I n vitro efficacy studies showed that the developed formulation increased TrkB receptor activity, leading to a decrease in BACE1 enzyme activity without any cytotoxic effect. In biodegradation studies, it was determined that nanomotor formulations exhibited increased retention in the brain with respect to the control group (p <0.05). Based on these studies, it has been concluded that designed memantine loaded nanomotors could be a promising novel approach for drug delivery in the treatment of Alzheimer's Disease.