Skip to main content
SpringerLink
Log in

Targeting Drugs into the Central Nervous System

  • Chapter
Book cover Biomedical Aspects of Drug Targeting

Abstract

Drugs face a formidable obstacle in reaching the central nervous systems (CNS) due to the existence and specific properties of the blood-brain barrier (BBB) that is a vital element in the regulation of the internal environment of the brain and the spinal cord. This chapter summarizes the principles and perspective of strategies that offer invasive and non-invasive approaches to overcome this major hurdle to the pharmacotherapy of the CNS.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Prokai, Laszlo. “Peptide drug delivery into the central nervous system.” In Progress in Drug Research, Vol. 51, E.M. Jucker, ed. Basel: Birkhäuser, 1998.

    Google Scholar 

  2. Brightman, Milton W. “Ultrastructure of brain endothelium,” In Physiology and Pharmacology of the Blood-Brain Barrier, Michael W.B. Bradbury, ed. Berlin: Springer-Verlag, 1992.

    Google Scholar 

  3. Dayson, H., Welch, K., Segal, M.B., The Physiology and Pathophysiology of the Cerebrospinal Fluid, Edinburgh, UK: Churchill Livingstone, 1987; pp. 105–118.

    Google Scholar 

  4. Crone, Christian. “The blood-brain barrier - facts and questions.” In Ion Homeostasis of the Brain, B.K. Siesjo, S.C. Sorensen, eds. Copenhagen: Munksgaard, 1971.

    Google Scholar 

  5. Tamai, I., Tsuji, A. Transporter-mediated permeation of drugs across the blood-brain barrier. J Pharm Sci 2000; 89: 1371–1388.

    Article  Google Scholar 

  6. Maness, L.M., Banks, W.A., Zadina, J.E., Kastin, A.J. Periventricular penetration and disappearance of ICV Tyr-MIF-1, DAMGO, tyrosine, and albumin. Peptides 1995; 17: 247–250.

    Article  Google Scholar 

  7. Pardridge, William M. Receptor-mediated peptide transport through the blood-brain barrier. Endocrine Rev 1986; 7: 314–330.

    Article  Google Scholar 

  8. Brownlees, J., Williams, C.H. Peptidases, peptides, and the mammalian blood-brain barrier. J Neurochem 1993; 60: 793–803.

    Article  Google Scholar 

  9. Tatsuta, T., Naito, M., Oh-Hara, T., Sugawara, I., Tsuruo, T. Functional involvement of P-glycoprotein in blood-brain barrier. J Biol Chem 1992; 28: 20383–20391.

    Google Scholar 

  10. Golden, P.L., Pardridge, W.M. Brain microvascular P-glycoprotein and a revised model of multidrug resistance in brain. Cell Mol Neurobiol 2000; 20: 165–81

    Article  Google Scholar 

  11. Munsat, T.L., Taft, J., Jackson, I.M.D., Andres, P.L., Hollander, D., Skerry, L., Ordman, M., Kasdon, D., Finison, L. Intrathecal thyrotropin-releasing hormone does not alter the progressive course of ALS: Experience with an intrathecal drug delivery system. Neurology 1992; 42: 1049–1053.

    Google Scholar 

  12. Passaro, E., Jr., Debas, H., Oldendorf, W., Yamada, T. Rapid appearance of intraventricularly administered neuropeptides in the peripheral circulation. Brain Res 1982; 241: 335–340.

    Article  Google Scholar 

  13. Domb, A.J., Ringel, I. Polymeric drug carrier systems in the brain. Methods Neurosci 1994; 21: 169–183.

    Google Scholar 

  14. Brem, J., Domb, A.J., Lenartz, D., Dureza, C., Olivi, A., Epstein, J.I. Brain biocompatibility of a biodegradable controlled release polymer consisting of anhydride copolymer of fatty acid dimer and sebacic acid. J Controlled Release 1992; 19: 325–329.

    Article  Google Scholar 

  15. Krewson, C.E., Saltzman, M. W. “Targeting of proteins in the brain following release from a polymer.” In Trends and Future Perspectives in Peptide and Protein Drug Delivery, V.H.L. Lee, M. Hashida, Y. Mizushima, eds. Chur (Switzerland): Harwood Academic Publishers, 1995.

    Google Scholar 

  16. Mendez, A., Camarata, P.J., Suryanarayanan, R., Ebner, T.J. Sustained intracerebral delivery of nerve growth factor with biodegradable polymer microspheres. Methods Neurosci 1994; 21: 150–168.

    Google Scholar 

  17. Bonetti, A., Kim, S. Pharmacokinetics of an extended-release human interferon alpha-2b formulation. Cancer Chemother Pharmacol 1993; 33: 258–261.

    Article  Google Scholar 

  18. Lysaght, M.J., Frydel, B., Gentile, F., Emerich, D., Winn, S. Recent progress in immunoisolated cell therapy. J Cell Biochem 1994; 196–203.

    Google Scholar 

  19. Rapoport, Stanley I. Osmotic opening of the blood-brain barrier: Principles, mechanism, and therapeutic applications. Cell Mol Neurobiol 2000; 20: 217–30.

    Google Scholar 

  20. Raymond, J.J., Robertson, D.M., Dinsdale, H.B. Pharmacological modification of bradykinin induced breakdown of the blood-brain barrier. Can J Neurol Sci 1986; 13: 214–220.

    Google Scholar 

  21. Habgood, M.D., Begley, D.J., Abbott, N.J. Determinants of passive drug entry into the central nervous system. Cell Mol Neurobiol 2000; 20: 231–253.

    Article  Google Scholar 

  22. Patel, Harish M. Liposomes: bags of challenge. Biochem Soc Trans 1984; 12: 333–335.

    Google Scholar 

  23. Bundgaard, Hans, Design of Pro-drugs. Amsterdam: Elsevier, 1985.

    Google Scholar 

  24. Prokai, L., Prokai-Tatrai, K., Bodor, N. Targeting drugs to the brain by redox chemical delivery systems. Med Res Rev 2000; 20: 367–416.

    Article  Google Scholar 

  25. Polt, R., Porreca, F., Szabo, L.Z., Bilsky, E.J., Davis, P., Abbruscato, T.J., Davis, T.P., Horvath, R., Yamamura, H.I., Hruby, V.J. Glycopeptide enkephalin analogs produce analgesia in mice–evidence for penetration of the blood-brain-barrier. Proc Natl Acad Sci USA 1994; 91: 7114–7118.

    Article  Google Scholar 

  26. Rousselle, C., Clair, P., Lefauconnier, J.-M., Kaczorek, M., Scherrmann, J.-M., Temsamani, J. New advances in the transport of doxorubicin through the blood-brain barrier by a peptide vector-mediated strategy. Mol Pharmacol 2000; 57: 679–686.

    Google Scholar 

  27. Pardridge, William M. Vector-mediated drug delivery to the brain. Adv Drug Deliv Rev. 1999; 36: 299–321.

    Article  Google Scholar 

  28. Shi, N.Y., Boado, R.J., Pardridge, W.M. Receptor-mediated gene targeting to tissues in vivo following intravenous administration of pegylated immunoliposomes. Pharm Res 2001; 18: 1091–1095.

    Article  Google Scholar 

  29. Kreuter, Jörg. Nanoparticulate systems for brain delivery of drugs. Adv Drug Deliv Rev 2001; 47: 65–81.

    Article  Google Scholar 

  30. Olivier, J.-C., Fenart, L., Chauvert, R., Pariat, C., Cecchelli, R., Couet, W. Indirect evidence that drug brain targeting using polysorbate 80-coated polybutylcyanoacrylate nanoparticles is related to toxicity. Pharm Res 1999; 16: 1836–1842.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Drug Discovery and Department of Pharmaceutics, College of Pharmacy, and the McKnight Brain Institute, University of Florida, Gainesville, FL, 32610-0497, USA

    Laszlo Prokai

Authors
  1. Laszlo Prokai
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Vladimir Muzykantov M.D., Ph.D.

  2. School of Pharmacy, Northeastern University, Boston, MA, USA

    Vladimir Torchilin Ph.D., D.Sc.

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer Science+Business Media New York

About this chapter

Cite this chapter

Prokai, L. (2002). Targeting Drugs into the Central Nervous System. In: Muzykantov, V., Torchilin, V. (eds) Biomedical Aspects of Drug Targeting. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-4627-3_19

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-4627-3_19

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-5312-4

  • Online ISBN: 978-1-4757-4627-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation