Beyond the blood–brain barrier: the fate of transcytosed therapeutics

H. Baghirov

doi:10.1016/j.tips.2025.08.006

Beyond the blood–brain barrier: the fate of transcytosed therapeutics

H. Baghirov

Research output: Contribution to journal › Review Article or Literature Review › peer-review

4 Citations (Scopus)

82 Downloads (Pure)

Abstract

Transcytosis across the blood–brain barrier (BBB) enables systemically administered large therapeutics to reach the brain parenchyma, but their fate in the parenchyma ultimately governs their therapeutic effect. Recent studies show that brain parenchymal cell uptake, internalization kinetics, reuptake at the BBB, and diffusion in the brain parenchyma shape the distribution and retention of therapeutics. Target engagement further influences their behavior beyond the BBB. These insights have prompted new strategies to enhance their distribution, retention, and target engagement. These include the selection of transport targets with favorable trafficking properties, the use of anchoring proteins, and modeling-based optimization. This opinion highlights emerging understanding of the fate of therapeutics in the brain parenchyma and outlines strategies to optimize this fate.

Original language	English
Pages (from-to)	946-957
Journal	Trends in Pharmacological Sciences
Volume	46
Issue number	10
DOIs	https://doi.org/10.1016/j.tips.2025.08.006
Publication status	Published - Oct 2025
MoE publication type	A2 Review article in a scientific journal

Keywords

blood–brain barrier
drug delivery
transcytosis
brain parenchyma
distribution
retention

Access to Document

10.1016/j.tips.2025.08.006

PIIS0165614725001828Final published version, 1.53 MBLicence: CC BY

https://urn.fi/URN:NBN:fi-fe20251205114788

Cite this

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title = "Beyond the blood{\textendash}brain barrier: the fate of transcytosed therapeutics",

abstract = "Transcytosis across the blood{\textendash}brain barrier (BBB) enables systemically administered large therapeutics to reach the brain parenchyma, but their fate in the parenchyma ultimately governs their therapeutic effect. Recent studies show that brain parenchymal cell uptake, internalization kinetics, reuptake at the BBB, and diffusion in the brain parenchyma shape the distribution and retention of therapeutics. Target engagement further influences their behavior beyond the BBB. These insights have prompted new strategies to enhance their distribution, retention, and target engagement. These include the selection of transport targets with favorable trafficking properties, the use of anchoring proteins, and modeling-based optimization. This opinion highlights emerging understanding of the fate of therapeutics in the brain parenchyma and outlines strategies to optimize this fate.",

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author = "H. Baghirov",

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language = "English",

volume = "46",

pages = "946--957",

journal = "Trends in Pharmacological Sciences",

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T1 - Beyond the blood–brain barrier: the fate of transcytosed therapeutics

AU - Baghirov, H.

PY - 2025/10

Y1 - 2025/10

N2 - Transcytosis across the blood–brain barrier (BBB) enables systemically administered large therapeutics to reach the brain parenchyma, but their fate in the parenchyma ultimately governs their therapeutic effect. Recent studies show that brain parenchymal cell uptake, internalization kinetics, reuptake at the BBB, and diffusion in the brain parenchyma shape the distribution and retention of therapeutics. Target engagement further influences their behavior beyond the BBB. These insights have prompted new strategies to enhance their distribution, retention, and target engagement. These include the selection of transport targets with favorable trafficking properties, the use of anchoring proteins, and modeling-based optimization. This opinion highlights emerging understanding of the fate of therapeutics in the brain parenchyma and outlines strategies to optimize this fate.

AB - Transcytosis across the blood–brain barrier (BBB) enables systemically administered large therapeutics to reach the brain parenchyma, but their fate in the parenchyma ultimately governs their therapeutic effect. Recent studies show that brain parenchymal cell uptake, internalization kinetics, reuptake at the BBB, and diffusion in the brain parenchyma shape the distribution and retention of therapeutics. Target engagement further influences their behavior beyond the BBB. These insights have prompted new strategies to enhance their distribution, retention, and target engagement. These include the selection of transport targets with favorable trafficking properties, the use of anchoring proteins, and modeling-based optimization. This opinion highlights emerging understanding of the fate of therapeutics in the brain parenchyma and outlines strategies to optimize this fate.

KW - blood–brain barrier

KW - drug delivery

KW - transcytosis

KW - brain parenchyma

KW - distribution

KW - retention

UR - https://www.scopus.com/pages/publications/105016733265

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DO - 10.1016/j.tips.2025.08.006

M3 - Review Article or Literature Review

SN - 0165-6147

VL - 46

SP - 946

EP - 957

JO - Trends in Pharmacological Sciences

JF - Trends in Pharmacological Sciences

IS - 10

ER -

Beyond the blood–brain barrier: the fate of transcytosed therapeutics

Abstract

Keywords

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NAP4DIVE: Non-Animal Platform for Nanoparticle-Based Delivery Across the Blood-Brain Barrier Interface with Vehicle Evolution

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Beyond the blood–brain barrier: the fate of transcytosed therapeutics

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Projects

NAP4DIVE: Non-Animal Platform for Nanoparticle-Based Delivery Across the Blood-Brain Barrier Interface with Vehicle Evolution

Cite this