Irinophore C鈩? a lipid-based nanoparticulate formulation of irinotecan, is more effective than free irinotecan when used to treat an orthotopic glioblastoma model

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• 作者：M. Verreault^a ; ^{mverreau@bccrc.ca} ; D. Strutt^a ; D. Masin^a ; M. Anantha^a ; D. Waterhouse^a ; D.T. Yapp^a ; ^b ; M.B. Bally^a ; ^b ; ^c ; ^d ; ^{mbally@bccrc.ca}
• 关键词：Glioblastoma ; Cancer ; Liposomes ; Irinotecan ; Drug delivery ; Tumor-associated vasculature
• 刊名：Journal of Controlled Release
• 出版年：2012
• 期刊代码：25_01683659
• 类别：pha
• 出版时间：28 February, 2012
• 卷：158
• 期：1
• 页码：34-43
• 文件大小：1109 K

摘要

Given compelling evidences supporting the therapeutic potential of irinotecan (IRN) for patients with glioblastoma (GBM), the present study evaluated the activity of Irinophore C鈩?(IrC鈩?, a lipid-based nanopharmaceutical formulation of IRN, in GBM. The levels of IRN and SN-38 were determined in plasma and brain after a single intravenous dose of IRN or IrC鈩?in tumor-free mice. Treatment with IrC鈩?significantly increased the plasma AUC_0-24 h of the active (lactone) forms of IRN and SN-38 when compared to free drug (760 and 30-fold increase, respectively). Levels of IRN and SN-38 in brain tissue were also increased significantly (compared to IRN treatment) following IrC鈩?administration. A tolerability study revealed that IrC鈩?is better tolerated than IRN. The efficacy of IrC鈩?and IRN was assessed in an orthotopic model of GBM. The therapeutic efficacy of IrC鈩?given at 25 mg/kg weekly was comparable to the efficacy achieved using twice the dose of IRN. At the maximum tolerated dose, IrC鈩?(100 mg/kg) increased the survival time of tumor-bearing mice of 83%compared to untreated animals. Ki67 immunostaining analysis of IrC鈩?treated tumors revealed a transient increase in cell proliferation after treatment. The results justify further studies evaluating the use of IrC鈩?for treating GBM.