Micellar and antibody-targeted polymer therapeutics

  • Etrych T
  • Chytil P
  • Kovář L
 et al. 
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Abstract

Synthesis, physicochemical and some biological properties of new actively targeted antibody-containing and passively targeted micellar polymer - doxorubicin conjugates were investigated. Polymer precursors used for the synthesis of the conjugates were based on semitelechelic N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers with reactive groups situated at the polymer chain end or on multivalent copolymer with groups randomly distributed along the polymer backbone. Micellar HPMA-copolymer-based pharmaceuticals were prepared by selfassembly of copolymer-doxorubicin conjugates containing hydrophobic cholesterol ligands attached to the copolymer via hydrolytically degradable spacer. pHControlled release of cholesterol derivative is a key-point for disintegration of the micellar drug carrier after delivering the drug to the tumor tissue. Synthesis of star antibody-targeted polymer conjugates takes advantage of reduction of disulfide bridges in antibody with dithiothreitol followed by conjugation with the semitelechelic copolymer thus avoiding modification of the binding site in the antibody for its antigen. Both conjugates differing in their molecular architecture and mechanism of action are promising candidates for in vivo antitumor therapy. Copyright © 2010 WILEY-VCH Verlag GmbH & Co.

Author-supplied keywords

  • Doxorubicin
  • Drug delivery systems
  • HPMA copolymers
  • Hydrazone bond
  • Monoclonal anti-CD20 antibody

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Authors

  • T. Etrych

  • P. Chytil

  • L. Kovář

  • B. Říhová

  • K. Ulbrich

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