Convection-enhanced delivery of polyethylene glycol-coated liposomal doxorubicin: Characterization and efficacy in rat intracranial glioma models: Laboratory investigation

Toshio Kikuchi, Ryuta Saito, Shin Ichirou Sugiyama, Yoji Yamashita, Toshihiro Kumabe, Michal Krauze, Krystof Bankiewicz, Teiji Tominaga

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

Object. The characteristics of polyethylene glycol-coated liposomal doxorubicin (PLD), the only liposomal drug now clinically available for intravenous injection, were investigated after convection-enhanced delivery (CED) into the rat brain parenchyma. Methods. The distribution, tissue retention, and toxicity profile were evaluated after CED into the rat brain parenchyma. The antitumor efficacy was also determined in rodent intracranial U-251MG and U-87MG glioma models. Results. Convection-enhanced delivery of PLD achieved wider distributions and delayed onset of toxicity in the brain parenchyma compared with CED of free doxorubicin infusion. Fluorescence generated from doxorubicin infused as PLD was detected until at least 30 days after infusion. Local toxicity was not observed when a 10% dilution of the commercially available PLD solution was used (0.2 mg/ml doxorubicin), but was significant at higher concentrations. Results after 10% PLD was delivered locally with CED demonstrated significant survival prolongation in both intracranial U-251MG and U-87MG xenograft models. Conclusions. Convection-enhanced delivery of PLD achieved extensive tissue distribution and sustained drug release. Convection-enhanced delivery of PLD is a promising chemotherapy for the treatment of malignant gliomas.

Original languageEnglish
Pages (from-to)867-873
Number of pages7
JournalJournal of neurosurgery
Volume109
Issue number5
DOIs
Publication statusPublished - 2008 Nov

Keywords

  • Chemotherapy
  • Convection-enhanced delivery
  • Glioma
  • Liposomal doxorubicin
  • Rat

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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