Zwitterionic pH-responsive hyaluronic acid polymer micelles for delivery of doxorubicin

Colloids Surf B Biointerfaces. 2019 Jun 1:178:412-420. doi: 10.1016/j.colsurfb.2019.03.007. Epub 2019 Mar 4.

Abstract

As zwitterionic polymers show great promise in drug delivery, hyaluronic acid (HA) was deacetylated and grafted with dodecylamine to prepare a pH-sensitive zwitterionic polymer dHAD used as a carrier for antitumor drugs. The polymer was negatively charged at pH 7.4 and became positive at pH 6.2. In vitro delivery of DOX against MCF-7 cells showed that the blank micelle dHAD had low cytotoxicity and the dHAD-DOX micelles could greatly prohibit the growth of the MCF-7 cells. In addition, the dHAD-DOX micelles had higher cellular uptake, indicating that the micelles were rapidly internalized into the cells via CD44 receptor-mediated endocytosis. The in vivo delivery of DOX to tumor-bearing mice confirmed that the dHAD-DOX micelles greatly inhibited the tumor growth and significantly reduced systemic toxicity of DOX. These results demonstrated that biocompatible pH-responsive zwitterionic dHAD micelles are promising carriers for the delivery of DOX.

Keywords: Biocompatibility; Drug delivery; Zwitterionic polymers; pH-responsiveness.

MeSH terms

  • Cell Survival / drug effects
  • Doxorubicin / chemistry*
  • Doxorubicin / pharmacology
  • Drug Delivery Systems / methods
  • Endocytosis / drug effects
  • Humans
  • Hyaluronic Acid / chemistry*
  • Hydrogen-Ion Concentration
  • MCF-7 Cells
  • Micelles
  • Polymers / chemistry*

Substances

  • Micelles
  • Polymers
  • Doxorubicin
  • Hyaluronic Acid