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Tissue-Specific Pharmacodelivery and Overcoming Key Cell Barriers in Vivo: Vascular Targeting of Caveolae

  • Lucy A. Carver
  • Jan E. Schnitzer
Chapter

Abstract

Molecular medicine has discovered many new therapeutic modalities using state-of-the art techniques in molecular biology. High through-put, in vitro assays that screen for pharmacological actions on the cell type of interest are frequently used in the design of new drugs. Although the potential for such agents is great and certainly justified by their success in vitro, they frequently perform much less effectively in vivo where the agent must reach its target cells in a tissue in sufficient quantities to be potent, while sparing bystander organs. Depending on the route of administration, the endothelium and/or epithelium form significant barriers that greatly limit the in vivo accessibility of many drugs, antibodies, and gene vectors to their intended target sites of pharmacological action, namely specific cells inside the tissue (1, 2). For example, poor tissue penetration has hindered the ability of many monoclonal antibodies to reach their cell-specific antigens and thus to achieve effective tissue- or cell-directed pharmaco-delivery in vivo (1–3). Understanding general and selective transport across key cell barriers to pharmaco-delivery in vivo is fundamental to achieving effective directed therapy. Moving the target from the tissue cell surface to the surface of the cell barrier, such as the vascular endothelium, has many theoretical advantages in tissue-specific delivery (4–7). The newly discovered molecular heterogeneity of endothelia among different tissues invites a new strategy of vascular targeting. Yet, this vascular targeting strategy still requires both validation in vivo and, to be useful for many therapies, a means by which to cross the vascular wall for access to underlying tissue cells (4). This chapter will not focus on all the elements and requirements for the “ideal” drug delivery system (for review, see (1)) but will be limited to an essential and critical component of access and getting intravenously injected agents specifically to a single tissue as well as inside the tissue across the endothelial cell border to the intended target cells.

Keywords

Endothelial Cell Surface Cell Barrier Vascular Target Endothelial Cell Barrier Biomedical Aspect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Lucy A. Carver
    • 1
  • Jan E. Schnitzer
    • 1
  1. 1.Sidney Kimmel Cancer CenterSan DiegoUSA

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