Preparation and biological properties of dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt)-loaded polymeric micelles.

Abstract

Block copolymer micelles, containing dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt), the oxaliplatin parent complex, were prepared through polymer-metal complex formation of DACHPt with poly(ethylene glycol)-poly(glutamic acid) block copolymer [PEG-P(Glu)] in distilled water. By dynamic light scattering (DLS) measurement, the micelle size was determined to be 40 nm with narrow distribution. The release of platinum complexes from the micelle core was measured in phosphate buffer saline (pH 7.4) at 37 degrees C. DACHPt-loaded micelle showed a sustained release rate of platinum after an induction period of 12 h. In the same conditions, the kinetic stability of DACHPt-loaded micelle was measured. The micelle was found to be very stable, keeping the initial size, for 240 h. Against murine colon adenocarcinoma 26 (C-26) cells, DACHPt-loaded micelle exhibited considerable in vitro cytotoxicity, lower than oxaliplatin but increasing with exposure time as a result of the release of platinum complexes from the micelle. In vivo biodistribution assay performed on tumor-bearing mice demonstrated that the micelle showed prolonged blood circulation due to its high stability and high tumor accumulation for a prolonged time.

• Authors: Horacio Cabral, Nobuhiro Nishiyama, Soichiro Okazaki, Hiroyuki Koyama, Kazunori Kataoka
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 101 Issue 1-3 Pg. 223-32 (Jan 03 2005) ISSN: 0168-3659 [Print] Netherlands
• PMID: 15588907 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Micelles
• Organoplatinum Compounds
• Polymers
• dichloro-1,2-diaminocyclohexane platinum complex

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Cell Line, Tumor
• Drug Delivery Systems
• Drug Stability
• Female
• Mice
• Micelles
• Organoplatinum Compounds (administration & dosage, chemistry, pharmacokinetics)
• Polymers (administration & dosage)