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

• The zwitterionic pH-responsive polymer micelles (dHAD) were synthesized for efficiently delivering DOX. • The dHAD micelles possessed excellent serum stability and very low cytotoxicity. • The pH-triggered charge-reversal of the dHAD-DOX micelles significantly improved the cellular uptake and cell growth inhibition. • The dHAD-DOX micelles exhibited antitumor therapeutic efficacy with remarkably low systemic toxicity in vivo. 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. [ABSTRACT FROM AUTHOR]