Thermosensitive micelles from PEG-based ether-anhydride triblock copolymers

Pharm Res. 2010 Aug;27(8):1627-43. doi: 10.1007/s11095-010-0155-1. Epub 2010 Apr 29.

Abstract

Purpose: The thermosensitive micelles based on the poly(PEG:CPP:SA) terpolymer composed of poly(ethylene glycol) (PEG), 1,3-bis(carboxyphenoxy) propane (CPP) and sebacic acid (SA) were fabricated for application as a promising drug carrier.

Methods: The terpolymer can self-assemble into micelles in water by a precipitation technology. The sol-gel transition behaviors were investigated by the tube-tilting method and dynamic rheology. The drug release behaviors were investigated in phosphate-buffered solution (PBS) at 25, 37 and 45 degrees C, respectively, and the tumor cell growth inhibition assays were also evaluated.

Results: The diameters of these micelles increased as the environmental temperature, and the length of CPP and SA chains increased. The micelles with a low concentration underwent sol-to-nanogel transition as temperature increased from the room temperature to the body temperature, while the polymer solutions with a high concentration underwent sol-to-gel transition as the temperature increased from 20 to 70 degrees C. In vitro release profiles consisted of a burst release followed a sustained release. The cytotoxicity results showed that the terpolymer micelles were biocompatible, and the encapsulated doxorubicin. HCl maintained its potent anti-tumor effect.

Conclusion: These micelles may bring the ether-anhydride family of polymers great potential as a novel carrier in nanomedicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anhydrides / chemical synthesis
  • Anhydrides / chemistry*
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Cells, Cultured
  • Doxorubicin / administration & dosage
  • Drug Delivery Systems*
  • Ethers / chemical synthesis
  • Ethers / chemistry*
  • Hep G2 Cells
  • Humans
  • Micelles*
  • Poloxamer / chemical synthesis
  • Poloxamer / chemistry*
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry*
  • Rats
  • Temperature*

Substances

  • Anhydrides
  • Antineoplastic Agents
  • Ethers
  • Micelles
  • Poloxamer
  • Polyethylene Glycols
  • Doxorubicin
  • pluronic L64