Synthesis of HPMA copolymer containing adriamycin bound via an acid- labile spacer and its activity toward human ovarian carcinoma cells

Won Moon Choi, Pavla Kopečková, Tamara Minko, Jindřich Kopeček

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer-adriamycin (ADR) conjugate (P-aconityl-ADR) was synthesized by the attachment of cis-aconityl- ADR to an HPMA copolymer precursor using 1-ethyl-3-(3- dimethylaminopropyl)carbodiimide (EDC) as the condensing agent. The ADR release from the HPMA copolymer conjugate was pH sensitive. After 48 h incubation at pH 5, 6, and 7, the amount of ADR released was 63.4, 9.2, and 2.8% respectively. The in vitro cytotoxicity of the conjugate was evaluated toward A2780 sensitive and A2780/AD resistant human ovarian carcinoma cells. An HPMA copolymer, containing ADR bound via a tetrapeptide (GFLG) sequence susceptible to cleavage catalyzed by lysosomal enzymes (P-GFLG-ADR), was used as control. The IC50 doses seemed to indicate that the total hydrolysis of P-aconityl-ADR in prelysosomal and lysosomal compartments proceeded faster than the release of ADR from P-GFLG-ADR catalyzed by lysomal cysteine proteinases. Both HPMA copolymer-ADR conjugates appeared to overcome the ATP- driven P-glycoprotein efflux pump expressed in A2780/AD cells.

Original languageEnglish (US)
Pages (from-to)447-456
Number of pages10
JournalJournal of Bioactive and Compatible Polymers
Volume14
Issue number6
DOIs
StatePublished - Nov 1999

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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