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Preparation and In Vivo Evaluation of Dichloro(1,2-Diaminocyclohexane)platinum(II)-Loaded Core Cross-Linked Polymer Micelles. 2012

Hardeep S Oberoi, and Natalia V Nukolova, and Yi Zhao, and Samuel M Cohen, and Alexander V Kabanov, and Tatiana K Bronich
Department of Pharmaceutical Sciences and Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198-5830, USA.

The therapeutic performance of oxaliplatin can be improved by incorporating the central cis-dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt) motif into the core cross-linked block copolymer micelles. We describe here the preparation, cellular uptake, and in vivo evaluation of core cross-linked micelles loaded with DACHPt. Stable drug-loaded micelles were prepared at high drug loading (~25 w/w%) and displayed a considerably increased in vitro cytotoxicity compared to free oxaliplatin against A2780 ovarian cancer cells. The DACHPt-loaded micelle formulation was well tolerated in mice and exhibited improved antitumor activity than oxaliplatin alone in an ovarian tumor xenograft model.

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