کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1424774 | 986738 | 2012 | 10 صفحه PDF | دانلود رایگان |
Given compelling evidences supporting the therapeutic potential of irinotecan (IRN) for patients with glioblastoma (GBM), the present study evaluated the activity of Irinophore C™ (IrC™), 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™ in tumor-free mice. Treatment with IrC™ significantly increased the plasma AUC0–24 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™ administration. A tolerability study revealed that IrC™ is better tolerated than IRN. The efficacy of IrC™ and IRN was assessed in an orthotopic model of GBM. The therapeutic efficacy of IrC™ given at 25 mg/kg weekly was comparable to the efficacy achieved using twice the dose of IRN. At the maximum tolerated dose, IrC™ (100 mg/kg) increased the survival time of tumor-bearing mice of 83% compared to untreated animals. Ki67 immunostaining analysis of IrC™-treated tumors revealed a transient increase in cell proliferation after treatment. The results justify further studies evaluating the use of IrC™ for treating GBM.
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Journal: Journal of Controlled Release - Volume 158, Issue 1, 28 February 2012, Pages 34–43