Novel pH sensitive block copolymer micelles for solvent free drug loading

Macromol Biosci. 2006 Feb 10;6(2):179-86. doi: 10.1002/mabi.200500182.

Abstract

Novel pH sensitive biodegradable block copolymers (MPEG-PDLLA-OSM) composed of mono-methoxy poly(ethylene glycol) (MPEG), poly (D,L-lactide) (PDLLA) and sulfamethazine oligomer (OSM) were synthesized via ring-opening polymerization and a dicyclohexyl carboimide (DCC) coupling reaction. These copolymers had a relatively low critical micelle concentration (CMC) due to the strong hydrophobic properties of non-ionized OSM at pH 7.0. Also, the pH sensitive block copolymers showed the micelle-unimer transition due to the ionization-non-ionization of OSM in the pH range (pH 7.2-8.4) above the CMC. Due to the pH sensitive properties of the block copolymer, the hydrophobic drug paclitaxel (PTX) was incorporated into a pH sensitive block copolymer micelle by the pH induced micellization method, without using an organic solvent. The block copolymer micelle prepared by pH induced micellization showed a relatively high PTX loading efficiency, and good stability for 2 d at 37 degrees C. Furthermore, the PTX loaded micelle showed a sustained release of PTX with a small burst in vitro over 2 d. The present results suggest that the pH induced micellization method due to the micelle-unimer transition of the pH sensitive block copolymer would be a novel and valuable drug incorporation tool for hydrophobic and protein drugs, since no organic solvent is involved in the formulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials / chemical synthesis
  • Biocompatible Materials / chemistry
  • Biodegradation, Environmental
  • Chromatography, High Pressure Liquid
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry*
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Light
  • Magnetic Resonance Spectroscopy
  • Materials Testing
  • Micelles
  • Paclitaxel / administration & dosage
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Scattering, Radiation
  • Solvents
  • Spectrophotometry

Substances

  • Biocompatible Materials
  • Drug Carriers
  • Micelles
  • Polymers
  • Solvents
  • Paclitaxel