Crossing the Blood–Brain Barrier: Innovations in Receptor- and Transporter-Mediated Transcytosis Strategies

The blood–brain barrier (BBB) is a highly selective and natural protective membrane that restricts the entry of therapeutic agents into the central nervous system (CNS). This restrictive nature poses a major challenge for pharmacological treatment of a wide range of CNS disorders, including neurodeg...

Full description

Saved in:
Bibliographic Details
Main Authors: Ling Ding, Pratiksha Kshirsagar, Prachi Agrawal, Daryl J. Murry
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/17/6/706
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850164763598782464
author Ling Ding
Pratiksha Kshirsagar
Prachi Agrawal
Daryl J. Murry
author_facet Ling Ding
Pratiksha Kshirsagar
Prachi Agrawal
Daryl J. Murry
author_sort Ling Ding
collection DOAJ
description The blood–brain barrier (BBB) is a highly selective and natural protective membrane that restricts the entry of therapeutic agents into the central nervous system (CNS). This restrictive nature poses a major challenge for pharmacological treatment of a wide range of CNS disorders, including neurodegenerative disorders, brain tumors, and psychiatric conditions. Many chemical drugs and biopharmaceuticals are unable to cross the BBB, and conventional drug delivery methods often fail to achieve sufficient brain concentrations, leading to reduced therapeutic efficacy and increased risk of systemic toxicity. In recent years, targeted drug delivery strategies have emerged as promising approaches to overcome the BBB and enhance the delivery of therapeutic agents to the brain. Among these, receptor-mediated transcytosis (RMT) and transporter-mediated transcytosis (TMT) are two of the most extensively studied mechanisms for transporting drugs across brain endothelial cells into the brain parenchyma. Advances in materials science and nanotechnology have facilitated the development of multifunctional carriers with optimized properties, improving drug targeting, stability, and release profiles within the brain. This review summarizes the physiological structure of the BBB and highlights recent innovations in RMT- and TMT-mediated brain drug delivery systems, emphasizing their potential not only to overcome current challenges in CNS drug development, but also to pave the way for next-generation therapies that enable more precise, effective, and personalized treatment of brain-related diseases.
format Article
id doaj-art-22fb4fe2a9fa41a19dd8ed1bd2d8ddea
institution OA Journals
issn 1999-4923
language English
publishDate 2025-05-01
publisher MDPI AG
record_format Article
series Pharmaceutics
spelling doaj-art-22fb4fe2a9fa41a19dd8ed1bd2d8ddea2025-08-20T02:21:53ZengMDPI AGPharmaceutics1999-49232025-05-0117670610.3390/pharmaceutics17060706Crossing the Blood–Brain Barrier: Innovations in Receptor- and Transporter-Mediated Transcytosis StrategiesLing Ding0Pratiksha Kshirsagar1Prachi Agrawal2Daryl J. Murry3Clinical Pharmacology Laboratory, Department of Pharmacy Practice and Science, University of Nebraska Medical Center, Omaha, NE 68198, USAClinical Pharmacology Laboratory, Department of Pharmacy Practice and Science, University of Nebraska Medical Center, Omaha, NE 68198, USAClinical Pharmacology Laboratory, Department of Pharmacy Practice and Science, University of Nebraska Medical Center, Omaha, NE 68198, USAClinical Pharmacology Laboratory, Department of Pharmacy Practice and Science, University of Nebraska Medical Center, Omaha, NE 68198, USAThe blood–brain barrier (BBB) is a highly selective and natural protective membrane that restricts the entry of therapeutic agents into the central nervous system (CNS). This restrictive nature poses a major challenge for pharmacological treatment of a wide range of CNS disorders, including neurodegenerative disorders, brain tumors, and psychiatric conditions. Many chemical drugs and biopharmaceuticals are unable to cross the BBB, and conventional drug delivery methods often fail to achieve sufficient brain concentrations, leading to reduced therapeutic efficacy and increased risk of systemic toxicity. In recent years, targeted drug delivery strategies have emerged as promising approaches to overcome the BBB and enhance the delivery of therapeutic agents to the brain. Among these, receptor-mediated transcytosis (RMT) and transporter-mediated transcytosis (TMT) are two of the most extensively studied mechanisms for transporting drugs across brain endothelial cells into the brain parenchyma. Advances in materials science and nanotechnology have facilitated the development of multifunctional carriers with optimized properties, improving drug targeting, stability, and release profiles within the brain. This review summarizes the physiological structure of the BBB and highlights recent innovations in RMT- and TMT-mediated brain drug delivery systems, emphasizing their potential not only to overcome current challenges in CNS drug development, but also to pave the way for next-generation therapies that enable more precise, effective, and personalized treatment of brain-related diseases.https://www.mdpi.com/1999-4923/17/6/706brain deliverytranscytosisblood–brain barriernanomaterials
spellingShingle Ling Ding
Pratiksha Kshirsagar
Prachi Agrawal
Daryl J. Murry
Crossing the Blood–Brain Barrier: Innovations in Receptor- and Transporter-Mediated Transcytosis Strategies
Pharmaceutics
brain delivery
transcytosis
blood–brain barrier
nanomaterials
title Crossing the Blood–Brain Barrier: Innovations in Receptor- and Transporter-Mediated Transcytosis Strategies
title_full Crossing the Blood–Brain Barrier: Innovations in Receptor- and Transporter-Mediated Transcytosis Strategies
title_fullStr Crossing the Blood–Brain Barrier: Innovations in Receptor- and Transporter-Mediated Transcytosis Strategies
title_full_unstemmed Crossing the Blood–Brain Barrier: Innovations in Receptor- and Transporter-Mediated Transcytosis Strategies
title_short Crossing the Blood–Brain Barrier: Innovations in Receptor- and Transporter-Mediated Transcytosis Strategies
title_sort crossing the blood brain barrier innovations in receptor and transporter mediated transcytosis strategies
topic brain delivery
transcytosis
blood–brain barrier
nanomaterials
url https://www.mdpi.com/1999-4923/17/6/706
work_keys_str_mv AT lingding crossingthebloodbrainbarrierinnovationsinreceptorandtransportermediatedtranscytosisstrategies
AT pratikshakshirsagar crossingthebloodbrainbarrierinnovationsinreceptorandtransportermediatedtranscytosisstrategies
AT prachiagrawal crossingthebloodbrainbarrierinnovationsinreceptorandtransportermediatedtranscytosisstrategies
AT daryljmurry crossingthebloodbrainbarrierinnovationsinreceptorandtransportermediatedtranscytosisstrategies