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Irinophore C™, 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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Title: Irinophore C™, a lipid-based nanoparticulate formulation of irinotecan, is more effective than free irinotecan when used to treat an orthotopic glioblastoma model
Authors: Verreault, M.1 mverreau@bccrc.ca, Strutt, D.1, Masin, D.1, Anantha, M.1, Waterhouse, D.1, Yapp, D.T.1,2, Bally, M.B.1,2,3,4 mbally@bccrc.ca
Source: Journal of Controlled Release. Feb2012, Vol. 158 Issue 1, p34-43. 10p.
Subjects: Nanoparticles, Lipids, Glioblastoma multiforme, Intravenous therapy, Drug efficacy, Cell proliferation
Abstract: Abstract: 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 AUC0–24h 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 25mg/kg weekly was comparable to the efficacy achieved using twice the dose of IRN. At the maximum tolerated dose, IrC™ (100mg/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. [Copyright &y& Elsevier]
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Database: Engineering Source
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Abstract:Abstract: 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 AUC0–24h 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 25mg/kg weekly was comparable to the efficacy achieved using twice the dose of IRN. At the maximum tolerated dose, IrC™ (100mg/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. [Copyright &y& Elsevier]
ISSN:01683659
DOI:10.1016/j.jconrel.2011.09.095