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Prodrugs for Liver-targeted Drug Delivery

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Prodrugs

Part of the book series: Biotechnology: Pharmaceutical Aspects ((PHARMASP,volume V))

Abstract

The liver is the organ in the body primarily responsible for maintaining a continuous supply of glucose, lipids, and other important metabolic substrates to peripheral tissues (Kahl, 1999). The liver also helps to control the circulating levels of certain amino acids, ketone bodies, free fatty acids, lipoproteins, and some hormones (e.g., insulin, steroids, T3) and plays an important role in the detoxification and excretion of various xenobiotics. Chronic liver diseases such as viral hepatitis and liver cancer, as well as some metabolic diseases associated with the liver such as non-alcoholic steatohepatitis, injure the liver. Chronic liver injury can lead sequentially to impaired liver function, liver failure, and death. Drugs for treating liver diseases are often limited by tolerability and extra-hepatic safety concerns, which prevent their use at maximally effective doses. Targeting drugs to the liver may circumvent some of these limitations and enable more effective therapies. This chapter reviews the liver-targeting strategies explored to date and, more specifically, the strengths and weaknesses of various prodrug strategies used for liver-specific drug delivery.

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Authors and Affiliations

  1. Metabasis Therapeutics, Inc., La Jolla, CA, 92037

    Mark D. Erion

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  1. Mark D. Erion
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Editors and Affiliations

  1. University of Kansas, Lawrence, KS, USA

    Valentino J. Stella  & Ronald T. Borchardt  & 

  2. Bristol-Myers Squibb Company, Princeton, NJ, USA

    Michael J. Hageman

  3. Gilead Sciences, Foster City, CA, USA

    Reza Oliyai

  4. Roche Palo Alto, LLC, Palo Alto, CA, USA

    Hans Maag

  5. Hoffmann-La Roche, Inc., Nutley, NJ, USA

    Jefferson W. Tilley

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© 2007 American Association of Pharmaceutical Scientists

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Erion, M.D. (2007). Prodrugs for Liver-targeted Drug Delivery. In: Stella, V.J., Borchardt, R.T., Hageman, M.J., Oliyai, R., Maag, H., Tilley, J.W. (eds) Prodrugs. Biotechnology: Pharmaceutical Aspects, vol V. Springer, New York, NY. https://doi.org/10.1007/978-0-387-49785-3_16

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