Development of boron nanotechnology based drug carriage system for the treatment of Alzheimer's disease

In recent years, the number of studies aiming for more effective and innovative treatment of devastating neurodegenerative diseases such as Alzheimer's has been increasing rapidly. In this thesis, a carrier system based on hexagonal boron nitride (hBN) attached to the surface of folic acid (FA) by esterification reaction was carried out. Detailed characterization studies were performed with SEM-EDX, UV-vis spectrum, FTIR and Zetasiezer analyzes for the prepared hBN-FA transport system. Toxicological evaluation of the delivery system was performed on human dermal fibroblast cell cultures. Memantine (MEM) and boron lipoic acid (BLA) loading and release profile of the hBN-FA transport system was evaluated, and then cytotoxicity analysis was performed by MTT assay on SHSY-5Y cells that were transformed into mature neuron-like cells via the use of retinoic acid. Drug loading results showed that non-coated hBN did not have the ability to load BLA, but showed a drug loading efficiency of 84,3% for MEM. On the other hand, the drug loading capacity of the hBN-FA delivery system for BLA and MEM was observed as 97,5% and 95%, respectively. Then, the in vitro Alzheimer's disease (AD) model was created with 20 µM Aβ(1-42) peptide in the differentiated SHSY-5Y cell culture, and the drug delivery potential of the drug-loaded transport system against Aβ(1-42) toxicity was evaluated. While hBN-FA+BLA showed 99% cell viability in the in vitro AD model, cell viability was calculated as 94% in the cell group treated with the same concentration of hBN-FA+MEM. Moreover, AChE activity determination, TAK and TOS analysis, Flow cytometry, and genotoxicity studies were correlated with cytotoxicity data. All findings showed that the neuroprotective effect of the drug delivery system, which has been evaluated for the first time in the in vitro experimental AD model, is a promising tool and provides important data for further research.