The piper at the gates of brain: A systematic review of surface modification strategies on lipid nanoparticles to overcome the Blood-Brain-Barrier

The Blood-Brain Barrier (BBB) significantly impedes drug delivery to the central nervous system. Nanotechnology, especially surface-functionalized lipid nanoparticles, offers innovative approaches to overcome this barrier. However, choosing an effective functionalization strategy is challenging due...

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Detalles Bibliográficos
Autores: Vargas, Ronny, Lizano-Barrantes, Catalina, Romero, Miguel, Valencia-Clua, Kevin, Narváez-Narváez, David A., Suñé-Negre, Josep Mª, Pérez-Lozano, Pilar, García-Montoya, Encarna, Martínez Martínez, Noelia, Hernández-Munaín, Cristina, Suñé, Carlos, Suñé-Pou, Marc
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/372543
Acceso en línea:http://hdl.handle.net/10261/372543
Access Level:acceso abierto
Palabra clave:Active targeting
Brain delivery
Nanoparticle decoration
Nanoparticle functionalization
Functionalization strategies
Receptor targeting
Ligand selection
Descripción
Sumario:The Blood-Brain Barrier (BBB) significantly impedes drug delivery to the central nervous system. Nanotechnology, especially surface-functionalized lipid nanoparticles, offers innovative approaches to overcome this barrier. However, choosing an effective functionalization strategy is challenging due to the lack of detailed comparative analysis in current literature. Our systematic review examined various functionalization strategies and their impact on BBB permeability from 2041 identified articles, of which 80 were included for data extraction. Peptides were the most common modification (18) followed by mixed strategies (12) proteins (9), antibodies (7), and other strategies (8). Interestingly, 26 studies showed BBB penetration with unmodified or modified nanoparticles using commonly applied strategies such as PEGylation or surfactant addition. Statistical analysis across 42 studies showed correlation between higher in vivo permeation improvements and nanoparticle type, size, and functionalization category. The highest ratios were found for nanostructured lipid carriers or biomimetic systems, in studies with particle sizes under 150 nm, and in those applying mixed functionalization strategies. The interstudy heterogeneity we observed highlights the importance of adopting standardized evaluation protocols to enhance comparability. Our systematic review aims to provide a comparative insight and identify future research directions in the development of more effective lipid nanoparticle systems for drug delivery to the brain to help improve the treatment of neurological and psychiatric disorders and brain tumours.