Journal ArticleDOI
Drug delivery through the blood-brain barrier
Ikumi Tamai,Akira Tsuji +1 more
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TLDR
In this article, specific mechanisms functioning at the blood-brain barrier (BBB) for the permeation of drugs and natural compounds in the bloodto-brain and brain-to-blood directions are described.About:
This article is published in Advanced Drug Delivery Reviews.The article was published on 1996-06-12. It has received 119 citations till now. The article focuses on the topics: Nanoparticles for drug delivery to the brain & Peptide transport.read more
Citations
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Journal ArticleDOI
The blood-brain and blood-tumor barriers: A review of strategies for increasing drug delivery
TL;DR: The relative advantages and disadvantages of the different methods of circumventing the blood-brain barrier are presented in this review, and special attention is given to convection-enhanced delivery, which has particular promise for the local delivery of large therapeutic agents such as monoclonal antibodies, antisense oligonucleotides, or viral vectors.
Patent
RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING CHEMICALLY MODIFIED SHORT INTERFERING NUCLEIC ACID (siNA)
James McSwiggen,Bharat Chowrira,Leonid Beigelman,Dennis G. Macejak,Shawn Zinnen,Pamela Pavco,Peter Haeberli,David Morrissey,Kathy Fosnaugh,Sharon Jamison,Nassim Usman,James Thompson,Chandra Vargeese,Weimin Wang,Tongqian Chen,Narendra K. Vaish +15 more
TL;DR: In this article, the authors present methods and reagents useful for modulating gene expression in various applications such as therapeutic, diagnostic, target assessment and genome discovery applications, which relates to synthetic chemically modified small nucleic acid molecules capable of mediating RNA interference (RNAi) to a target NCA sequence, such as short interfering nucleic acids (siNA), short interfering RNA (siRNA).
Journal ArticleDOI
CNS Drug Design Based on Principles of Blood‐Brain Barrier Transport
TL;DR: It is important to merge CNS drug discovery and CNS drug delivery as early as possible in the overall CNS drug development process to avoid termination caused by negligible blood‐brain barrier transport.
Journal ArticleDOI
Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1
Ikumi Tamai,Hikaru Yabuuchi,Jun Ichi Nezu,Yoshimichi Sai,Asuka Oku,Miyuki Shimane,Akira Tsuji +6 more
TL;DR: Although its subcellular localization and detailed functional characteristics are not clear at present, OCTN1 appears to be a novel proton antiporter that functions for active secretion of cationic compounds across the renal epithelial brush‐border membrane and may play a role in the renal excretion of xenobiotics and their metabolites.
Journal ArticleDOI
Transporter-mediated permeation of drugs across the blood-brain barrier
Ikumi Tamai,Akira Tsuji +1 more
TL;DR: To identify the transporters functional at the BBB and to examine the possible involvement of them in drug transports by molecular and physiological approaches will provide a rational basis for controlling drug distribution to the brain.
References
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Journal ArticleDOI
A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants.
TL;DR: Observations on the molecular basis of pleiotropic drug resistance are interpreted in terms of a model wherein certain surface glycoproteins control drug permeation by modulating the properties of hydrophobic membrane regions.
Journal ArticleDOI
Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues
Franz Thiebaut,Takashi Tsuruo,Hirofumi Hamada,Michael M. Gottesman,Ira Pastan,Mark C. Willingham +5 more
TL;DR: The results suggest that the protein has a role in the normal secretion of metabolites and certain anti-cancer drugs into bile, urine, and directly into the lumen of the gastrointestinal tract.
Journal ArticleDOI
Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs
Alfred H. Schinkel,J. J. M. Smit,O. van Tellingen,Jos H. Beijnen,Els Wagenaar,L. Van Deemter,C. A. A. M. Mol,M. A. Van Der Valk,E. Robanus-Maandag,H te Riele,Anton Berns,Piet Borst +11 more
TL;DR: The findings explain some of the side effects in patients treated with a combination of carcinostatics and P-glycoprotein inhibitors and indicate that these inhibitors might be useful in selectively enhancing the access of a range of drugs to the brain.
Journal ArticleDOI
The biochemistry of P-glycoprotein-mediated multidrug resistance.
Jane A. Endicott,Ling +1 more
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Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites.
Carlos Cordon-Cardo,James P. O'Brien,Dolors Casals,Lana Rittman-Grauer,June L. Biedler,Myron R. Melamed,Joseph R. Bertino +6 more
TL;DR: P-glycoprotein expression in capillary endothelium of brain and testes and not other tissues (i.e., kidney and placenta) may in part explain this phenomenon and could have important implications in cancer chemotherapy.