Drug delivery across the blood-brain barrier: why is it difficult? how to measure and improve it?

Expert Opinion on Drug Delivery
Yaming Su, Patrick J Sinko

Abstract

The development of drugs that act in the CNS has been significantly impeded by the difficulty of delivering them across the blood-brain barrier (BBB). This article aims to provide the reader with a critical overview of important issues in the discovery and development of drugs that need to enter the brain to elicit pharmacological activity, focusing particularly on i) the role of drug transporters in brain permeation and how to manipulate them to enhance drug brain bioavailability; ii) the successful application, limitations and challenges of commonly used in vitro and in vivo methodologies for measuring drug transport across the BBB, and iii) a discussion of recently developed strategies (e.g., modulation of efflux transporters by chemical inhibitors and the employment of delivery vectors taking advantage of native transport systems at the BBB) for facilitating drug penetration into the brain.

References

Nov 11, 1976·Biochimica Et Biophysica Acta·R L Juliano, V Ling
Jan 1, 1992·Progress in Brain Research·J RauhH J Galla
May 1, 1992·Journal of Neurochemistry·M P DehouckJ P Tillement
Dec 1, 1991·The Journal of Cell Biology·L L RubinJ Morales
May 1, 1990·Journal of Neurochemistry·M P DehouckR Cecchelli
Jan 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·C Cordon-CardoJ R Bertino
Apr 1, 1989·Journal of Neuroscience Research·D Z GerhartL R Drewes
Jun 1, 1985·Journal of Neurochemistry·W M PardridgeJ Yang
Sep 1, 1987·Metabolism: Clinical and Experimental·W M PardridgeJ Yang
Oct 1, 1987·The Journal of Cell Biology·G van MeerK Simons
Mar 29, 1985·Science·G L King, S M Johnson
Jul 1, 1967·The Journal of Cell Biology·T S Reese, M J Karnovsky
Feb 18, 1981·Biochimica Et Biophysica Acta·J C RichardsonN L Simmons
Jun 3, 1982·Brain Research·C Crone, S P Olesen
Mar 1, 1994·Brain Research. Molecular Brain Research·R J BoadoW M Pardridge
May 1, 1996·Pharmaceutical Research·S C BasakL R Drewes
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·J HuwylerW M Pardridge
Jan 1, 1997·The Journal of Clinical Investigation·P L GoldenW M Pardridge
Mar 1, 1997·Journal of Neurochemistry·W M PardridgeU Bickel
Nov 21, 1997·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A MuruganandamD B Stanimirovic
Jan 15, 1998·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·E M CornfordA V Delgado-Escueta
Sep 17, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·E K RowinskyD D Von Hoff

❮ Previous
Next ❯

Citations

Jan 9, 2009·Breast Cancer Research and Treatment·Renata DuchnowskaCezary Szczylik
Oct 29, 2008·Pharmaceutical Research·Mei-Ling Chen, Vincent H L Lee
Jul 21, 2012·Biochemistry. Biokhimii︠a︡·N GoldsteinS Terterov
Oct 6, 2012·Therapeutic Delivery·Neelima ManthaNandita G Das
Dec 30, 2011·Brain Structure & Function·Sylvia Van DorpeBart De Spiegeleer
Sep 10, 2014·Expert Opinion on Drug Safety·Giovanni FalisiRaul Quezada Arcega
Feb 6, 2008·Expert Opinion on Drug Delivery·Giovanni TosiMaria Angela Vandelli
May 14, 2009·Expert Opinion on Drug Delivery·Eugen BarbuDariusz C Górecki
Apr 1, 2007·Expert Opinion on Drug Discovery·Marianne A GrantAlan C Rigby
Jun 25, 2015·Artificial Cells, Nanomedicine, and Biotechnology·Devendra SinghNeeraj Mishra
Aug 11, 2011·International Journal of Pharmaceutics·Paolo BlasiMaurizio Ricci
Apr 18, 2008·The Journal of Pharmacy and Pharmacology·Matthias BrandschEva Bosse-Doenecke
Oct 31, 2014·AAPS PharmSciTech·Jigar LalaniAmbikanandan Misra
Jan 8, 2014·Clinical Microbiology Reviews·Timothy FeltonWilliam W Hope
Feb 10, 2018·Annals of Botany·Diego F E EscobarLeonor Patricia C Morellato
Mar 3, 2020·Drug Metabolism Reviews·Faheem Hyder PottooGhulam Md Ashraf
Jun 28, 2013·American Journal of Physiology. Cell Physiology·Sara Seabrooke, Michael J O'Donnell
Dec 5, 2021·AAPS PharmSciTech·Nkafu Bechem NdemazieEdward Agyare

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood-Brain Barrier Transport in Neurodegeneration

The blood brain barrier is important for regulating the movement of biomolecules in and out of the brain. For example, membrane transporters in the blood brain barrier can be essential for regulating drug movement and dysregulation of these processes may play a role in neurodegeneration. This feed follows the latest research on this topic.