TY - JOUR
T1 - Convection-enhanced delivery of polyethylene glycol-coated liposomal doxorubicin
T2 - Characterization and efficacy in rat intracranial glioma models: Laboratory investigation
AU - Kikuchi, Toshio
AU - Saito, Ryuta
AU - Sugiyama, Shin Ichirou
AU - Yamashita, Yoji
AU - Kumabe, Toshihiro
AU - Krauze, Michal
AU - Bankiewicz, Krystof
AU - Tominaga, Teiji
PY - 2008/11
Y1 - 2008/11
N2 - 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.
AB - 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.
KW - Chemotherapy
KW - Convection-enhanced delivery
KW - Glioma
KW - Liposomal doxorubicin
KW - Rat
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U2 - 10.3171/JNS/2008/109/11/0867
DO - 10.3171/JNS/2008/109/11/0867
M3 - Article
C2 - 18976076
AN - SCOPUS:58149163011
VL - 109
SP - 867
EP - 873
JO - Journal of Neurosurgery
JF - Journal of Neurosurgery
SN - 0022-3085
IS - 5
ER -