title: Cisplatin-loaded core cross-linked micelles: comparative pharmacokinetics, antitumor activity, and toxicity in mice.
abstract: 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.
authors: Department of Pharmaceutical Sciences and Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198-5830, USA.
authors: Hardeep S
authors: HS
authors: Oberoi
authors: Natalia V
authors: NV
authors: Nukolova
authors: Frederic C
authors: FC
authors: Laquer
authors: Larisa Y
authors: LY
authors: Poluektova
authors: Jiangeng
authors: J
authors: Huang
authors: Yazen
authors: Y
authors: Alnouti
authors: Masanao
authors: M
authors: Yokohira
authors: Lora L
authors: LL
authors: Arnold
authors: Alexander V
authors: AV
authors: Kabanov
authors: Samuel M
authors: SM
authors: Cohen
authors: Tatiana K
authors: TK
authors: Bronich
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008823:Micelles; D050997:Nanomedicine; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D014018:Tissue Distribution / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D011109:Polymethacrylic Acids; D011092:Polyethylene Glycols; D002945:Cisplatin