Evidence mapPaperPMID 41012505Full record

ReviewPharmaceutics2025

Cracking the Blood-Brain Barrier Code: Rational Nanomaterial Design for Next-Generation Neurological Therapies.

Lucio Nájera-Maldonado, Mariana Parra-González, Esperanza Peralta-Cuevas, Ashley J Gutierrez-Onofre, Igor Garcia-Atutxa, Francisca Villanueva-Flores

Abstract readReview
In one paragraph

Review in Pharmaceutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  14. Research progress of stem cells in the treatment of atherosclerosis.Frontiers in cell and developmental biology · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Lucio Nájera-MaldonadoCentro de Investigación en Ciencia Aplicada y Tecnología Avanzada (CICATA) Unidad Morelos del Instituto Politécnico Nacional (IPN), Boulevard de la Tecnología No. 1036, Xochitepec 62790, Mexico.
Mariana Parra-GonzálezCentro de Investigación en Ciencia Aplicada y Tecnología Avanzada (CICATA) Unidad Morelos del Instituto Politécnico Nacional (IPN), Boulevard de la Tecnología No. 1036, Xochitepec 62790, Mexico.ORCID 0009-0006-6055-0428
Esperanza Peralta-CuevasCentro de Investigación en Ciencia Aplicada y Tecnología Avanzada (CICATA) Unidad Morelos del Instituto Politécnico Nacional (IPN), Boulevard de la Tecnología No. 1036, Xochitepec 62790, Mexico.ORCID 0009-0001-7785-9599
Ashley J Gutierrez-OnofreCentro de Investigación en Ciencia Aplicada y Tecnología Avanzada (CICATA) Unidad Morelos del Instituto Politécnico Nacional (IPN), Boulevard de la Tecnología No. 1036, Xochitepec 62790, Mexico.
Igor Garcia-AtutxaDepartamento de Ciencias de la Computación, Universidad Católica de Murcia (UCAM), Av. de los Jerónimos, 135, 30107 Murcia, Spain.ORCID 0009-0002-1551-2685
Francisca Villanueva-FloresCentro de Investigación en Ciencia Aplicada y Tecnología Avanzada (CICATA) Unidad Morelos del Instituto Politécnico Nacional (IPN), Boulevard de la Tecnología No. 1036, Xochitepec 62790, Mexico.ORCID 0000-0001-6092-4211

Funding

Instituto Politécnico Nacional SIP20242814Instituto Politécnico Nacional SIP20250306Instituto Politécnico Nacional SIP20251096Instituto Politécnico Nacional SIP20254781
6 · The paper itself

Abstract

This review provides a mechanistic framework to strategically design nanoparticles capable of efficiently crossing the blood-brain barrier (BBB), a critical limitation in neurological treatments. We systematically analyze nanoparticle-BBB transport mechanisms, including receptor-mediated transcytosis, adsorptive-mediated transcytosis, and transient barrier modulation. Essential nanoparticle parameters (size, shape, stiffness, surface charge, and biofunctionalization) are evaluated for their role in enhancing brain targeting. For instance, receptor-targeted nanoparticles can significantly enhance brain uptake, achieving levels of up to 17.2% injected dose per gram (ID/g) in preclinical glioma models. Additionally, validated preclinical models (human-derived in vitro systems, rodents, and non-human primates) and advanced imaging techniques crucial for assessing nanoparticle performance are discussed. Distinct from prior BBB nanocarrier reviews that primarily catalogue mechanisms, this work (i) derives quantitative 'design windows' (size 10-100 nm, aspect ratio ~2-5, near-neutral ζ) linked to transcytosis efficiency, (ii) cross-walks human-relevant in vitro/in vivo models (including TEER thresholds and NHP evidence) into a translational decision guide, and (iii) integrates regulatory/toxicology readiness (ISO 10993-4, FDA/EMA, ICH) into practical checklists. We also curate recent (2020-2025) %ID/g brain-uptake data across lipidic, polymeric, protein, inorganic, and hybrid vectors to provide actionable, evidence-based rules for BBB design.

Indexed as

blood–brain barrierCNS drug deliverynanomedicinenanoparticleneurotherapeutics

Identifiers

PMID41012505
PMCPMC12473768

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.