title: Convection-enhanced delivery of polyethylene glycol-coated liposomal doxorubicin: characterization and efficacy in rat intracranial glioma models.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Ryuta
authors.initials: R
authors.lastname: Saito
authors.forename: Shin-ichirou
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Yoji
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kumabe
authors.forename: Michal
authors.initials: M
authors.lastname: Krauze
authors.forename: Krystof
authors.initials: K
authors.lastname: Bankiewicz
authors.forename: Teiji
authors.initials: T
authors.lastname: Tominaga
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D018481:Convection; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D011092:Polyethylene Glycols; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D011092:Polyethylene Glycols; D004317:Doxorubicin