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A new era in brain drug delivery: Integrating multivalency and computational optimisation for blood–brain barrier permeation

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Efficient drug delivery across the blood–brain barrier (BBB) remains a significant obstacle in treating central nervous system (CNS) disorders. This review provides an in-depth analysis of the structural and molecular mechanisms underlying BBB integrity and its functional properties. We detail the role of key cellular and molecular components that regulate selective molecular transport across the barrier, alongside a description of the current therapeutic approaches for brain drug delivery, including those leveraging receptor-mediated transcytosis. Emphasis is placed on multivalency-based strategies that enhance the specificity of nanoparticle targeting and improve transport efficacy across the BBB. Additionally, we discuss the added value of integrating mathematical and computational models with experimental validation for accelerating BBB-targeted delivery systems optimisation.

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Advanced Drug Delivery Reviews, 2025, vol. 224, 115637

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cc-by (c) Porro, Giulia Maria et al., 2025

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Articles publicats en revistes (Física de la Matèria Condensada)

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A new era in brain drug delivery: Integrating multivalency and computational optimisation for blood–brain barrier permeation