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Surface-modified lipid nanocarriers for crossing the blood-brain barrier (BBB): A current overview of active targeting in brain diseases

Teixeira, Maria Inês, Lopes, Carla M., Amaral, Maria Helena, Costa, Paulo C.·2023·Colloids and Surfaces B: Biointerfaces
DOI 10.1016/j.colsurfb.2022.112999
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Abstract

The blood-brain barrier (BBB) restricts the access of therapeutic agents to the brain, complicating the treatment of neurological diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), glioma, etc. To overcome this limitation and improve drug delivery to the central nervous system (CNS), the potential of nanocarriers, including lipid-based nanosystems, has been explored. Through active targeting, the surface of the nanocarriers can be modified with ligands that interact with the BBB, enhancing their uptake and penetration across the brain endothelium by different physiological mechanisms, such as receptor- or transporter-mediated transcytosis. This review seeks to provide an overview of active targeting in brain delivery, while highlighting the potential of functionalized lipid nanocarriers to treat brain diseases. Therefore, in the first sections, we discuss the importance of active targeting in CNS drug delivery, present the different ligands commonly used for functionalization, as well as summarize the state of the art of the most recent and relevant studies of surface-modified lipid nanosystems developed for neurological disorders. Lastly, challenges hindering clinical translation are discussed, and critical insights and future perspectives outlined. Although some limitations have been identified, it is expected that in the upcoming years these nanosystems will be an established approach.

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  • Using conjugates such as lipid nanoparticles or other delivery vehicles facilitates transport of modified microRNAs across the blood-brain barrier, promoting efficient uptake and sustained therapeutic effects.

    “Finally, using conjugates, such as lipid nanoparticles or other delivery vehicles, facilitates the transport of modified microRNAs across the blood-brain barrier, a critical step in reaching the target cells within the CNS, thus promoting the efficient uptake and sustained therapeutic effects.203,204”

    From MiR-128-3p – a gray eminence of the human central nervous system (2024) · cites this paper as [203]

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Metadata

Authors
Teixeira, M. I., Lopes, C. M., Amaral, M. H., & Costa, P. C.
Venue
Colloids and Surfaces B: Biointerfaces
Publisher
Elsevier BV
Published
2023-01
Volume
221
Pages
112999
ISSN
0927-7765
DOI
10.1016/j.colsurfb.2022.112999
Cited by
154
References
11
Language
en
Licence
Funders
Fundação para a Ciência e a Tecnologia (LA/P/0140/2020, UIDP/04378/2020, UIDB/04378/2020, 2020.05060)

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