Navigating Neurotoxicity and Safety Assessment of Nanocarriers for Brain Delivery: Strategies and Insights

• Type: Another Publication in an International Scientific Journal
• Date: 2024

Authors

Teixeira, MI (Author) Other; Lopes, CM (Author) Other; Maria Helena Amaral (Author) FFUP; Paulo Costa (Author) FFUP

Journal

Title: Acta Biomaterialia

Vol. 189

Pages: 25-56

ISSN: 1742-7061

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-017-7BG

DOI: 10.1016/j.actbio.2024.09.027

Abstract (EN): Nanomedicine, an area that uses nanomaterials for theragnostic purposes, is advancing rapidly, particularly in the detection and treatment of neurodegenerative diseases. The design of nanocarriers can be optimized to enhance drug bioavailability and targeting to specific organs, improving therapeutic outcomes. However, clinical translation hinges on biocompatibility and safety. Nanocarriers can cross the blood-brain barrier (BBB), potentially causing neurotoxic effects through mechanisms such as oxidative stress, DNA damage, and neuroinflammation. Concerns about their accumulation and persistence in the brain make it imperative to carry out a nanotoxicological risk assessment. Generally, this involves identifying exposure sources and routes, characterizing physicochemical properties, and conducting cytotoxicity assays both in vitro and in vivo . The lack of a specialized regulatory framework creates substantial gaps, making it challenging to translate findings across development stages. Additionally, there is a pressing need for innovative testing methods due to constraints on animal use and the demand for high-throughput screening. This review examines the mechanisms of nanocarrier-induced neurotoxicity and the challenges in risk assessment, highlighting the impact of physicochemical properties and the advantages and limitations of current neurotoxicity evaluation models. Future perspectives are also discussed. Additional guidance is crucial to improve the safety of nanomaterials and reduce associated uncertainty. Statement of significance Nanocarriers show tremendous potential for theragnostic purposes in neurological diseases, enhancing drug targeting to the brain, and improving biodistribution and pharmacokinetics. However, their neurotoxicity is still a major field to be explored, with only 5% of nanotechnology-related publications addressing this matter. This review focuses on the issue of neurotoxicity and safety assessment of nanocarriers for brain delivery. Neurotoxicity-relevant exposure sources, routes, and molecular mechanisms, along with the impact of the physicochemical properties of nanomaterials, are comprehensively described. Moreover, the different experimental models used for neurotoxicity evaluation are explored at length, including their main advantages and limitations. To conclude, we discuss current challenges and future perspectives for a better understanding of risk assessment of nanocarriers for neurobiomedical applications. (c) 2024 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 32