Cisplatin-loaded core cross-linked micelles: comparative pharmacokinetics, antitumor activity, and toxicity in mice

Hardeep S Oberoi,1 Natalia V Nukolova,1,2 Frederic C Laquer,3 Larisa Y Poluektova,4 Jiangeng Huang,1 Yazen Alnouti,1 Masanao Yokohira,5 Lora L Arnold,5 Alexander V Kabanov,1,2 Samuel M Cohen,5 Tatiana K Bronich,1,21Department of Pharmaceutical Sciences and Center for Drug Delivery and Nanomedicine,...

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Autores principales:	Oberoi HS, Nukolova NV, Laquer FC, Poluektova LY, Huang J, Alnouti Y, Yokohira M, Arnold LL, Kabanov AV, Cohen SM, Bronich TK
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d17236a38e0344eca05a6c656421ca4e
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spelling	oai:doaj.org-article:d17236a38e0344eca05a6c656421ca4e2021-12-02T06:46:36ZCisplatin-loaded core cross-linked micelles: comparative pharmacokinetics, antitumor activity, and toxicity in mice1176-91141178-2013https://doaj.org/article/d17236a38e0344eca05a6c656421ca4e2012-06-01T00:00:00Zhttp://www.dovepress.com/cisplatin-loaded-core-cross-linked-micelles-comparative-pharmacokineti-a10066https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Hardeep S Oberoi,1 Natalia V Nukolova,1,2 Frederic C Laquer,3 Larisa Y Poluektova,4 Jiangeng Huang,1 Yazen Alnouti,1 Masanao Yokohira,5 Lora L Arnold,5 Alexander V Kabanov,1,2 Samuel M Cohen,5 Tatiana K Bronich,1,21Department of Pharmaceutical Sciences and Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA; 2Department of Chemistry, MV Lomonosov Moscow State University, Leninskie Gory, Moscow, Russia; 3Department of Chemistry, University of Nebraska at Omaha, 4Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 5Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USAAbstract: Polymer micelles with cross-linked ionic cores are shown here to improve the therapeutic performance of the platinum-containing anticancer compound cisplatin. Biodistribution, antitumor efficacy, and toxicity of cisplatin-loaded core cross-linked micelles of poly(ethylene glycol)-b-poly(methacrylic acid) were evaluated in a mouse ovarian cancer xenograft model. Cisplatin-loaded micelles demonstrated prolonged blood circulation, increased tumor accumulation, and reduced renal exposure. Improved antitumor response relative to free drug was seen in a mouse model. Toxicity studies with cisplatin-loaded micelles indicate a significantly improved safety profile and lack of renal abnormalities typical of free cisplatin treatment. Overall, the study supports the fundamental possibility of improving the potential of platinum therapy using polymer micelle-based drug delivery.Keywords: cross-linked micelle, cisplatin, ovarian cancer, block ionomer complex, drug deliveryOberoi HSNukolova NVLaquer FCPoluektova LYHuang JAlnouti YYokohira MArnold LLKabanov AVCohen SMBronich TKDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 2557-2571 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Oberoi HS Nukolova NV Laquer FC Poluektova LY Huang J Alnouti Y Yokohira M Arnold LL Kabanov AV Cohen SM Bronich TK Cisplatin-loaded core cross-linked micelles: comparative pharmacokinetics, antitumor activity, and toxicity in mice
description	Hardeep S Oberoi,1 Natalia V Nukolova,1,2 Frederic C Laquer,3 Larisa Y Poluektova,4 Jiangeng Huang,1 Yazen Alnouti,1 Masanao Yokohira,5 Lora L Arnold,5 Alexander V Kabanov,1,2 Samuel M Cohen,5 Tatiana K Bronich,1,21Department of Pharmaceutical Sciences and Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA; 2Department of Chemistry, MV Lomonosov Moscow State University, Leninskie Gory, Moscow, Russia; 3Department of Chemistry, University of Nebraska at Omaha, 4Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 5Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USAAbstract: Polymer micelles with cross-linked ionic cores are shown here to improve the therapeutic performance of the platinum-containing anticancer compound cisplatin. Biodistribution, antitumor efficacy, and toxicity of cisplatin-loaded core cross-linked micelles of poly(ethylene glycol)-b-poly(methacrylic acid) were evaluated in a mouse ovarian cancer xenograft model. Cisplatin-loaded micelles demonstrated prolonged blood circulation, increased tumor accumulation, and reduced renal exposure. Improved antitumor response relative to free drug was seen in a mouse model. Toxicity studies with cisplatin-loaded micelles indicate a significantly improved safety profile and lack of renal abnormalities typical of free cisplatin treatment. Overall, the study supports the fundamental possibility of improving the potential of platinum therapy using polymer micelle-based drug delivery.Keywords: cross-linked micelle, cisplatin, ovarian cancer, block ionomer complex, drug delivery
format	article
author	Oberoi HS Nukolova NV Laquer FC Poluektova LY Huang J Alnouti Y Yokohira M Arnold LL Kabanov AV Cohen SM Bronich TK
author_facet	Oberoi HS Nukolova NV Laquer FC Poluektova LY Huang J Alnouti Y Yokohira M Arnold LL Kabanov AV Cohen SM Bronich TK
author_sort	Oberoi HS
title	Cisplatin-loaded core cross-linked micelles: comparative pharmacokinetics, antitumor activity, and toxicity in mice
title_short	Cisplatin-loaded core cross-linked micelles: comparative pharmacokinetics, antitumor activity, and toxicity in mice
title_full	Cisplatin-loaded core cross-linked micelles: comparative pharmacokinetics, antitumor activity, and toxicity in mice
title_fullStr	Cisplatin-loaded core cross-linked micelles: comparative pharmacokinetics, antitumor activity, and toxicity in mice
title_full_unstemmed	Cisplatin-loaded core cross-linked micelles: comparative pharmacokinetics, antitumor activity, and toxicity in mice
title_sort	cisplatin-loaded core cross-linked micelles: comparative pharmacokinetics, antitumor activity, and toxicity in mice
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/d17236a38e0344eca05a6c656421ca4e
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Cisplatin-loaded core cross-linked micelles: comparative pharmacokinetics, antitumor activity, and toxicity in mice

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