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dc.contributor.authorHuo, Tianyao-
dc.contributor.authorBarth, Rolf F.-
dc.contributor.authorYang, Weiliang-
dc.contributor.authorNakkula, Robin J.-
dc.contributor.authorKoynova, Rumiana D.-
dc.contributor.authorTenchov, Boris G.-
dc.contributor.authorRay-Chaudhury, Abhik-
dc.contributor.authorAgius, Lawrence M.-
dc.contributor.authorBoulikas, Teni-
dc.contributor.authorElleaume, Hélène-
dc.contributor.authorLee, Robert Jian Guang-
dc.identifier.citationHuo, T., Barth, R. F., Yang, W., Nakkula, R. J., Koynova, R., Tenchov, B.,...Lee, R. J. (2012). Preparation, biodistribution and neurotoxicity of liposomal cisplatin following convection enhanced delivery in normal and F98 glioma bearing rats. PLoS ONE, 7(11), e48752.en_GB
dc.description.abstractThe purpose of this study was to evaluate two novel liposomal formulations of cisplatin as potential therapeutic agents for treatment of the F98 rat glioma. The first was a commercially produced agent, Lipoplatin™, which currently is in a Phase III clinical trial for treatment of non-small cell lung cancer (NSCLC). The second, produced in our laboratory, was based on the ability of cisplatin to form coordination complexes with lipid cholesteryl hemisuccinate (CHEMS). The in vitro tumoricidal activity of the former previously has been described in detail by other investigators. The CHEMS liposomal formulation had a Pt loading efficiency of 25% and showed more potent in vitro cytotoxicity against F98 glioma cells than free cisplatin at 24 h. In vivo CHEMS liposomes showed high retention at 24 h after intracerebral (i.c.) convection enhanced delivery (CED) to F98 glioma bearing rats. Neurotoxicologic studies were carried out in non-tumor bearing Fischer rats following i.c. CED of Lipoplatin™ or CHEMS liposomes or their "hollow" counterparts. Unexpectedly, Lipoplatin™ was highly neurotoxic when given i.c. by CED and resulted in death immediately following or within a few days after administration. Similarly "hollow" Lipoplatin™ liposomes showed similar neurotoxicity indicating that this was due to the liposomes themselves rather than the cisplatin. This was particularly surprising since Lipoplatin™ has been well tolerated when administered intravenously. In contrast, CHEMS liposomes and their "hollow" counterparts were clinically well tolerated. However, a variety of dose dependent neuropathologic changes from none to severe were seen at either 10 or 14 d following their administration. These findings suggest that further refinements in the design and formulation of cisplatin containing liposomes will be required before they can be administered i.c. by CED for the treatment of brain tumors and that a formulation that may be safe when given systemically may be highly neurotoxic when administered directly into the brain.en_GB
dc.subjectCisplatin -- Testingen_GB
dc.subjectLiposomes -- Therapeutic useen_GB
dc.subjectGliomas -- Chemotherapyen_GB
dc.subjectPlatinum compounds -- Therapeutic useen_GB
dc.subjectBrain -- Tumors -- Chemotherapyen_GB
dc.subjectCancer -- Chemotherapyen_GB
dc.titlePreparation, biodistribution and neurotoxicity of liposomal cisplatin following convection enhanced delivery in normal and F98 glioma bearing ratsen_GB
dc.rights.holderThe copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder.en_GB
dc.publication.titlePLoS ONEen_GB
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