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

[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 (TM) (IrC (TM)), 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 (TM) in tumor-free mice. Treatment with IrC (TM) 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 (TM) administration. A tolerability study revealed that IrC (TM) is better tolerated than IRN. The efficacy of IrC (TM) and IRN was assessed in an orthotopic model of GBM. The therapeutic efficacy of IrC (TM) given at 25 mg/kg weekly was comparable to the efficacy achieved using twice the dose of IRN. At the maximum tolerated dose, IrC (TM) (100 mg/kg) increased the survival time of tumor-bearing mice of 83% compared to untreated animals. Ki67 immunostaining analysis of IrC (TM)-treated tumors revealed a transient increase in cell proliferation after treatment. The results justify further studies evaluating the use of IrC (TM) for treating GBM. (c) 2011 Elsevier B.V. All rights reserved.

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