title: Anticancer drug delivery systems: multi-loaded N4-acyl poly(ethylene glycol) prodrugs of ara-C. II. Efficacy in ascites and solid tumors.
abstract: The synthesis of branched PEG (40,000) acids has been achieved using aspartic acid (Asp) and AspAsp dendrons. Complete conjugation of these dendritic acids with cytosine arabinoside (ara-C) was achieved by the use of spacers that allowed a greater separation of the branches to accommodate several large ara-C molecules in proximity to each other. The tetrameric and octameric PEG-ara-C amide prodrugs were much more effective in the treatment of solid and ascites tumors compared to the native drug. The greater loading of the PEG backbone appears to have achieved a minimum threshold concentration for the therapeutic delivery of ara-C.
authors.affiliation: Enzon, Inc., 20 Kingsbridge Road, Piscataway, NJ 08854-3969, USA.
authors.forename: Yun H
authors.initials: YH
authors.lastname: Choe
authors.forename: Charles D
authors.initials: CD
authors.lastname: Conover
authors.forename: Dechun
authors.initials: D
authors.lastname: Wu
authors.forename: Maksim
authors.initials: M
authors.lastname: Royzen
authors.forename: Yoany
authors.initials: Y
authors.lastname: Gervacio
authors.forename: Virna
authors.initials: V
authors.lastname: Borowski
authors.forename: Mary
authors.initials: M
authors.lastname: Mehlig
authors.forename: Richard B
authors.initials: RB
authors.lastname: Greenwald
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D003561:Cytarabine / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods* / Q000706:statistics & numerical data; D004354:Drug Screening Assays, Antitumor / Q000379:methods / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry; D012997:Solvents / Q000008:administration & dosage; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays / Q000379:methods / Q000706:statistics & numerical data
chemical_list: D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D012997:Solvents; D003561:Cytarabine; D011092:Polyethylene Glycols