Anticancer drug delivery systems: N4-acyl poly(ethyleneglycol) prodrugs of ara-C. I. Efficacy in solid tumors.
A systematic study of N(4) amino PEG-prodrugs of ara-C (1) was conducted and provided a series of disubstituted amides, as well as a carbamate derivative. These conjugates showed hydrolysis half lives in rat plasma from about 1 h to 3 days, but were stable for >24 h in phosphate buffer, pH 7.4. In an LX-1 solid lung tumor model some of the PEG prodrugs exhibited superior activity to ara-C when compared on a molar basis. One problematic issue that was identified in this investigation was the need to increase the loading of ara-C onto PEG in order to avoid highly viscous solutions.
Choe
Yun H
YH
Enzon, Inc., 20 Kingsbridge Road, Piscataway, NJ 08854-3969, USA.
Conover
Charles D
CD
Wu
Dechun
D
Royzen
Maksim
M
Greenwald
Richard B
RB
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D003561:Cytarabine / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods* / Q000706:statistics & numerical data; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry; D012997:Solvents / Q000008:administration & dosage / Q000737:chemistry; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays / Q000379:methods / Q000706:statistics & numerical data
D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D012997:Solvents; D003561:Cytarabine; D011092:Polyethylene Glycols