A smart flower-like polymeric micelle for pH-triggered anticancer drug release

Int J Pharm. 2009 Jun 22;375(1-2):163-9. doi: 10.1016/j.ijpharm.2009.04.005. Epub 2009 Apr 11.

Abstract

Novel pH-responsive flower-like micelles were developed to provide the mechanism for pH-triggered drug release from drug carriers. The micelles (particle size: approximately 165 nm; critical micelle concentration (CMC): approximately 4 microg/ml), constructed from poly(N(epsilon)-(3-diethylamino)propyl isothiocyanato-L-lysine)-b-poly(ethylene glycol)-b-poly(L-lactide) [poly(DEAP-Lys)-b-PEG-b-PLLA], were designed to have a self-assembled flower-like arrangement consisting of two hydrophobic blocks [deprotonated poly(DEAP-Lys) block and PLLA block] and a petal-like hydrophilic PEG block at physiological pH. As the pH decreases to slightly acidic pH (<pH 7.0), as in tumor extracellular pH (pH(e)), the flower-like micelles undergo a change in the hydrophobicity of the micellar core. The protonation of poly(DEAP-Lys) changed the physical property of the polymer from hydrophobic to hydrophilic, resulting in disintegration of the micellar core. The co-presence of a pH-insensitive PLLA block in the micellar core affected the protonation of poly(DEAP-Lys), allowing the micelle to be stable at pH 7.0-7.4. In this study using doxorubicin (DOX) as the model drug, DOX release from the micelles accelerated in response to tumor pH(e).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / chemistry
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Drug Delivery Systems
  • Hydrogen-Ion Concentration
  • Hydrophobic and Hydrophilic Interactions
  • Lactic Acid / chemistry
  • Micelles
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Particle Size
  • Polyesters
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry*

Substances

  • Antibiotics, Antineoplastic
  • Micelles
  • Polyesters
  • Polymers
  • Lactic Acid
  • Polyethylene Glycols
  • poly(lactide)
  • Doxorubicin