Convection-enhanced delivery of polyethylene glycol-coated liposomal doxorubicin: characterization and efficacy in rat intracranial glioma models.
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.
Kikuchi
Toshio
T
Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Saito
Ryuta
R
Sugiyama
Shin-ichirou
S
Yamashita
Yoji
Y
Kumabe
Toshihiro
T
Krauze
Michal
M
Bankiewicz
Krystof
K
Tominaga
Teiji
T
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
D000903:Antibiotics, Antineoplastic; D011092:Polyethylene Glycols; D004317:Doxorubicin