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Antibody-targeted cyclosporin A

Authors
Journal
Journal of Controlled Release
0168-3659
Publisher
Elsevier
Publication Date
Volume
19
Identifiers
DOI: 10.1016/0168-3659(92)90063-w
Keywords
  • Antibody-Targeted Cyclosporin A
  • Transplanted Patients
  • Synthetic Copolymer Hpma
  • Immunosuppression
Disciplines
  • Biology
  • Medicine
  • Pharmacology

Abstract

Abstract The aim of this study was to test the pharmacological effectiveness of antibody-targeted cyclosporin A. Only free drug is currently available; its administration is accompanied by nephrotoxicity, hepatotoxicity and neurotoxicity which severely limits the treatment. Moreover, due to the high nonspecific binding to a number of tissues, the therapeutic doses are considerably higher than required for the actual treatment. We suggest using antibody-targeted CsA conjugate based on a water-soluble synthetic copolymer of N-(2-hydroxypropyl)methacrylamide to overcome these problems. In this construct the antibody to T lymphocyte subsets (anti-CD3 in human and anti-Thy 1.2 in mouse) is responsible for the specific delivery which limits the drug action to the target tissue. Antibody-targeted CsA effectively inhibits lectin- and alloantigen-induced T cell proliferation and considerably reduces CsA nephrotoxicity.

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