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Boron Nitride Nanoparticles Loaded with a Boron-Based Hybrid as a Promising Drug Carrier System for Alzheimer's Disease Treatment
Erzurum Tech Univ, Dept Mol Biol & Genet, TR-25050 Erzurum, Turkey..
Erzurum Tech Univ, Dept Mol Biol & Genet, TR-25050 Erzurum, Turkey..ORCID iD: 0000-0002-1600-2305
Erzurum Tech Univ, Dept Mol Biol & Genet, TR-25050 Erzurum, Turkey..
Univ G dAnnunzio, Dept Pharm, Via Vestini 31, I-66100 Chieti, Italy..ORCID iD: 0000-0001-6253-0443
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2022 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 15, article id 8249Article in journal (Refereed) Published
Abstract [en]

The search for an innovative and effective drug delivery system that can carry and release targeted drugs with enhanced activity to treat Alzheimer's disease has received much attention in the last decade. In this study, we first designed a boron-based drug delivery system for effective treatment of AD by integrating the folic acid (FA) functional group into hexagonal boron nitride (hBN) nanoparticles (NPs) through an esterification reaction. The hBN-FA drug carrier system was assembled with a new drug candidate and a novel boron-based hybrid containing an antioxidant as BLA, to constitute a self-assembled AD nano transport system. We performed molecular characterization analyses by using UV-vis spectroscopy, Fourier transform infrared spectrophotometer (FTIR), scanning electron microscope (SEM), Energy-dispersive X-ray spectroscopy (EDS) and Zeta potential investigations. Second, we tested the anti-Alzheimer properties of the carrier system on a differentiated neuroblastoma (SHSY5-Y) cell line, which was exposed to beta-amyloid (1-42) peptides to stimulate an experimental in vitro AD model. Next, we performed cytotoxicity analyses of synthesized molecules on the human dermal fibroblast cell line (HDFa) and the experimental AD model. Cytotoxicity analyses showed that even higher concentrations of the carrier system did not enhance the toxicological outcome in HDFa cells. Drug loading analyses reported that uncoated hBN nano conjugate could not load the BLA, whereas the memantine loading capacity of hBN was 84.3%. On the other hand, memantine and the BLA loading capacity of the hBN-FA construct was found to be 95% and 97.5%, respectively. Finally, we investigated the neuroprotective properties of the nano carrier systems in the experimental AD model. According to the results, 25 mu g/mL concentrations of hBN-FA+memantine (94% cell viability) and hBN-FA+BLA (99% cell viability) showed ameliorative properties against beta-amyloid (1-42) peptide toxicity (50% cell viability). These results were generated through the use of flow cytometry, acetylcholinesterase (AChE) and antioxidant assays. In conclusion, the developed drug carrier system for AD treatment showed promising potential for further investigations and enlightened neuroprotective capabilities of boron molecules to treat AD and other neurodegenerative diseases. On the other hand, enzyme activity, systematic toxicity analyses, and animal studies should be performed to understand neuroprotective properties of the designed carrier system comprehensively.

Place, publisher, year, edition, pages
MDPI , 2022. Vol. 23, no 15, article id 8249
Keywords [en]
hexagonal boron nitride, folic acid, boron lipoic acid, Alzheimer's disease, experimental Alzheimer's disease model
National Category
Neurosciences Manufacturing, Surface and Joining Technology Materials Chemistry
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URN: urn:nbn:se:kth:diva-316732DOI: 10.3390/ijms23158249ISI: 000839274100001PubMedID: 35897815Scopus ID: 2-s2.0-85135379612OAI: oai:DiVA.org:kth-316732DiVA, id: diva2:1691410
Note

QC 20220830

Available from: 2022-08-30 Created: 2022-08-30 Last updated: 2022-09-07Bibliographically approved

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Mardinoglu, Adil

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