Boron Nitride Nanoparticles Loaded with a Boron-Based Hybrid as a Promising Drug Carrier System for Alzheimer’s Disease Treatment

Abstract

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 µg/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.

Ameliorative Effects by Hexagonal Boron Nitride Nanoparticles against Beta Amyloid Induced Neurotoxicity

“…According to these results, hBN-NPs were found to have protective potential against toxicity by Aβ. In addition, IL-1β and TNF-α played key roles in astrocyte iNOS Aβ stimulation and necrosis contained TRAF6-, TRAF2- and NIK from the signaling mechanisms [ 66 , 67 ]. Deregulation of apoptosis was shown to play a role in the pathogenesis of various diseases involving neurodegenerative diseases, ischemic damage, autoimmune diseases and cancer.…”

Lipoic Acid Conjugated Boron Hybrids Enhance Wound Healing and Antimicrobial Processes

“…Based on cytotoxicity analyses, we found that hBN-ALA and B 4 C-ALA nanoparticles exhibit low-level toxicity on the fibroblast cell line and there was no cell viability difference under 50 µg/mL concentrations of hBN-ALA and B 4 C-ALA applications compared to the negative control. Previous studies have also shown that hBN and B 4 C nanoparticles do not elevate cytotoxicity in different types of cell culture under certain treatment concentrations [ 14 , 15 , 25 , 26 , 27 , 28 , 29 ]. Besides, antioxidant treatments have been shown to exhibit accelerating features that have been previously used in wound-healing treatment studies [ 30 , 31 , 32 , 33 ].…”

“…A concentration of 0.5 mg/mL of ALA was attached onto the hBN and B 4 C particles by the esterification reaction. The reaction was carried out with minor modifications of our previous work [ 14 ]. Briefly, 30 mg of hBN and B 4 C were mixed with 30 mL HNO 3 for 1 h and stirred overnight.…”

In Vitro Transcriptome Analysis of Cobalt Boride Nanoparticles on Human Pulmonary Alveolar Cells

“…Moreover, chitosan nanoparticles that have been proposed as an effective drug delivery system were claimed to exhibit cytotoxic properties at the concentration of 2 mg/mL against the conjunctival cell line [ 32 ]. Furthermore, in our recent study, folic acid-conjugated boron nitride nanoparticles (FA-BN NPs) were proposed as an effective and self-assembling drug delivery system for Alzheimer’s disease (AD) treatment [ 7 ]. In the study, boron lipoic acid (BLA)- and memantine (MEM)-loaded FA-BN NPs showed promising drug delivery and release potential in the experimental AD models.…”

“…Hence, different types of nanomaterial are widely used in the medical and food sectors as well as in the cosmetics field in the form of liposomes, nanosomes, inorganic compounds, dendrimers, and metals [ 2 , 3 , 4 , 5 ]. Considering the important and inalienable functions of nanosized materials in variegated sectors, it becomes inevitable to investigate their toxicological properties by using different approaches, including cytotoxic, genotoxic, and toxicogenomic analysis [ 6 , 7 , 8 , 9 ].…”