TY - JOUR
T1 - Synthesis of HPMA copolymer containing adriamycin bound via an acid- labile spacer and its activity toward human ovarian carcinoma cells
AU - Choi, Won Moon
AU - Kopečková, Pavla
AU - Minko, Tamara
AU - Kopeček, Jindřich
PY - 1999/11
Y1 - 1999/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0344129078&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0344129078&partnerID=8YFLogxK
U2 - https://doi.org/10.1177/088391159901400601
DO - https://doi.org/10.1177/088391159901400601
M3 - Article
VL - 14
SP - 447
EP - 456
JO - Journal of Bioactive and Compatible Polymers
JF - Journal of Bioactive and Compatible Polymers
SN - 0883-9115
IS - 6
ER -