Synthesis and antitumour activity of medium molecular weight phthalimide polymers of camptothecin

Attachment of anticancer agents to polymers has been demonstrated to improve their therapeutic profiles. A new monomer containing camptothecin, 5-norbonene-endo-2,3-dicarboxylimidoundecanoyl-camptothecin (NDUCPT) and its homopolymer and copolymer with acrylic acid (AA) were synthesized and spectroscopically characterized. The NDUCPT content in poly(NDUCPT-co-AA) obtained by elemental analysis was 51%. The average molecular weights of the polymers determined by gel permeation chromatography were as follows: M-n = 12 100, M-w = 23 400 g mol(-1), M-w/M-n = 1.93 for poly(NDUCPT), M-n = 15 400, M-w = 28 300 g mol(-1), M-w/M-n = 1.83 for poly(NDUCPT-co-AA). The IC50 value of NDUCPT and its polymers against U937 cancer cells was larger than that of CPT. The in vivo antitumour activity of all polymers in Balb/C mice bearing the sarcoma 180 tumour cell line was greater than that of CPT at a dose of 100 mg kg(-1). (C) 2003 Society of Chemical Industry.