Local delivery of doxorubicin for the treatment of malignant brain tumors in rats

Anticancer Res. Nov-Dec 2005;25(6B):3825-31.

Abstract

Background: Local delivery of carmustine (BCNU) via biodegradable polymers has been shown to improve survival in patients with glioblastoma multiforme (GBM). In the current study, we hypothesized that local delivery of an anthracycline antibiotic, doxorubicin (DOX), might act to improve the survival of animals bearing experimental intracranial glioma.

Materials and methods: Polyanhydride polymers (PCPP-SA), containing either 3% or 5% ADR by weight, were prepared using the mix-melt method. Forty male Fisher 344 rats received an intracranial challenge with a lethal dose of 9L gliosarcoma cells. Five days later, they received DOX or blank polymer. There were a total of four treatment groups: (1) blank polymer; (2) 3% DOX polymer; (3) 5% DOX polymer, and (4) control group with no polymer.

Results: Compared to control animals treated with no polymers or blank polymer, animals receiving DOX had significantly extended survival. The median survival for the control group was 21 days vs. 34 days (p < 0.01) for the 3% DOX group and 45 days (p < 0.0001) for the 5% DOX group.

Conclusion: Doxorubicin, when delivered locally, is an effective monotherapeutic agent against experimental intracranial glioma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / toxicity
  • Biocompatible Materials / administration & dosage
  • Biocompatible Materials / toxicity
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Decanoic Acids / administration & dosage*
  • Decanoic Acids / toxicity
  • Delayed-Action Preparations
  • Doxorubicin / administration & dosage*
  • Doxorubicin / toxicity
  • Drug Carriers / administration & dosage
  • Drug Carriers / toxicity
  • Drug Implants
  • Female
  • Gliosarcoma / drug therapy*
  • Gliosarcoma / pathology
  • Polyesters / administration & dosage*
  • Polyesters / toxicity
  • Rats
  • Rats, Inbred F344

Substances

  • Antibiotics, Antineoplastic
  • Biocompatible Materials
  • Decanoic Acids
  • Delayed-Action Preparations
  • Drug Carriers
  • Drug Implants
  • Polyesters
  • Doxorubicin
  • decanedioic acid-4,4'-(1,3-propanediylbis(oxy))bis(benzoic acid) copolymer