Anticancer drug delivery systems: N4-acyl poly(ethyleneglycol) prodrugs of ara-C. I. Efficacy in solid tumors

J Control Release. 2002 Feb 19;79(1-3):41-53. doi: 10.1016/s0168-3659(01)00469-2.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / chemistry
  • Cytarabine / administration & dosage*
  • Cytarabine / chemistry
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / statistics & numerical data
  • Drug Evaluation, Preclinical / methods
  • Drug Evaluation, Preclinical / statistics & numerical data
  • Female
  • Humans
  • Leukemia P388 / drug therapy
  • Mice
  • Mice, Nude
  • Neoplasms / drug therapy
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / chemistry
  • Prodrugs / administration & dosage*
  • Prodrugs / chemistry
  • Solvents / administration & dosage
  • Solvents / chemistry
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays* / methods
  • Xenograft Model Antitumor Assays* / statistics & numerical data

Substances

  • Antimetabolites, Antineoplastic
  • Prodrugs
  • Solvents
  • Cytarabine
  • Polyethylene Glycols