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Drug Delivery and Translational Research

, Volume 8, Issue 4, pp 883–902 | Cite as

Targeting therapeutics to endothelium: are we there yet?

  • Raisa Yu. Kiseleva
  • Patrick M. Glassman
  • Colin F. Greineder
  • Elizabeth D. Hood
  • Vladimir V. Shuvaev
  • Vladimir R. Muzykantov
Review Article

Abstract

Vascular endothelial cells represent an important therapeutic target in many pathologies, including inflammation, oxidative stress, and thrombosis; however, delivery of drugs to this site is often limited by the lack of specific affinity of therapeutics for these cells. Selective delivery of both small molecule drugs and therapeutic proteins to the endothelium has been achieved through the use of targeting ligands, such as monoclonal antibodies, directed against endothelial cell surface markers, particularly cell adhesion molecules (CAMs). Careful selection of target molecules and targeting agents allows for precise delivery to sites of inflammation, thereby maximizing therapeutic drug concentrations at the site of injury. A good understanding of the physiological and pathological determinants of drug and drug carrier pharmacokinetics and biodistribution may allow for a priori identification of optimal properties of drug carrier and targeting agent. Targeted delivery of therapeutics such as antioxidants and antithrombotic agents to the injured endothelium has shown efficacy in preclinical models, suggesting the potential for translation into clinical practice. As with all therapeutics, demonstration of both efficacy and safety are required for successful clinical implementation, which must be considered not only for the individual components (drug, targeting agent, etc.) but also for the sum of the parts (e.g., the drug delivery system), as unexpected toxicities may arise with complex delivery systems. While the use of endothelial targeting has not been translated into the clinic to date, the preclinical results summarized here suggest that there is hope for successful implementation of these agents in the years to come.

Keywords

Vascular immunotargeting Endothelial targeting Drug delivery Antioxidants Antithrombotic drugs 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Controlled Release Society 2017

Authors and Affiliations

  • Raisa Yu. Kiseleva
    • 1
  • Patrick M. Glassman
    • 1
  • Colin F. Greineder
    • 1
  • Elizabeth D. Hood
    • 1
  • Vladimir V. Shuvaev
    • 1
  • Vladimir R. Muzykantov
    • 1
  1. 1.Department of Pharmacology, The Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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