Filamentous, mixed micelles of triblock copolymers enhance tumor localization of indocyanine green in a murine xenograft model

Mol Pharm. 2012 Jan 1;9(1):135-43. doi: 10.1021/mp200381c. Epub 2011 Dec 12.

Abstract

Polymeric micelles formed by the self-assembly of amphiphilic block copolymers can be used to encapsulate hydrophobic drugs for tumor-delivery applications. Filamentous carriers with high aspect ratios offer potential advantages over spherical carriers, including prolonged circulation times. In this work, mixed micelles composed of poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) (PEO-PHB-PEO) and Pluronic F-127 (PF-127) were used to encapsulate a near-infrared fluorophore. The micelle formulations were assessed for tumor accumulation after tail vein injection to xenograft tumor-bearing mice by noninvasive optical imaging. The mixed micelle formulation that facilitated the highest tumor accumulation was shown by cryo-electron microscopy to be filamentous in structure compared to spherical structures of pure PF-127 micelles. In addition, increased dye loading efficiency and dye stability were attained in this mixed micelle formulation compared to pure PEO-PHB-PEO micelles. Therefore, the optimized PEO-PHB-PEO/PF-127 mixed micelle formulation offers advantages for cancer delivery over micelles formed from the individual copolymer components.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemical Phenomena
  • Contrast Media / administration & dosage*
  • Contrast Media / analysis
  • Contrast Media / pharmacokinetics
  • Drug Carriers / administration & dosage*
  • Drug Carriers / analysis
  • Drug Carriers / pharmacokinetics
  • Drug Compounding
  • Drug Stability
  • Humans
  • Indocyanine Green / administration & dosage*
  • Indocyanine Green / analysis
  • Indocyanine Green / pharmacokinetics
  • Injections, Intravenous
  • Male
  • Melanoma, Experimental / diagnosis*
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Micelles
  • Poloxamer / chemistry*
  • Polyethylene Glycols / chemistry*
  • Specific Pathogen-Free Organisms
  • Spectroscopy, Near-Infrared
  • Tissue Distribution
  • Whole Body Imaging

Substances

  • Contrast Media
  • Drug Carriers
  • Micelles
  • poly(ethylene oxide)-poly(3-hydroxybutyrate)-poly(ethylene oxide)
  • Poloxamer
  • Polyethylene Glycols
  • Indocyanine Green