title: Irinophore C™, a lipid-based nanoparticulate formulation of irinotecan, is more effective than free irinotecan when used to treat an orthotopic glioblastoma model.
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 AUC(0-24h) 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.
authors: Experimental Therapeutics, British Columbia Cancer Agency, 675 West 10th Avenue, Vancouver, BC, Canada. mverreau@bccrc.ca
authors: M
authors: M
authors: Verreault
authors: D
authors: D
authors: Strutt
authors: D
authors: D
authors: Masin
authors: M
authors: M
authors: Anantha
authors: D
authors: D
authors: Waterhouse
authors: D T
authors: DT
authors: Yapp
authors: M B
authors: MB
authors: Bally
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000077146:Irinotecan; D008081:Liposomes; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D000077146:Irinotecan; D002166:Camptothecin