Multifunctional micelles self-assembled from hyaluronic acid conjugate for enhancing anti-tumor effect of paclitaxel

Abstract

The clinical application of paclitaxel (PTX) is limited due to its low solubility and severe side effects. In this study, an amphiphilic graft copolymer based on mPEG, deoxycholic acid and N-acetyl-L-cysteine modified hyaluronic acid (mPEG-HA(DCA)-NAC) was synthesized and used as a redox-sensitive nano-sized drug delivery system. The polymer was characterized by Fourier transform infrared (FT-IR) and Proton nuclear magnetic resonance (1H NMR) analysis. As an amphiphilic polymer, mPEG-HA(DCA)-NAC could self-assemble into micelles in aqueous milieu and encapsulate PTX in the hydrophobic core with high drug loading of 15.6% and high encapsulation efficiency of 73.8%. The PTX-loaded micelles had an average size of 147 nm and zeta potential of −38.3 mV. Physicochemical properties of the micelles were measured by TEM and XRD analysis. XRD analysis confirmed the successful encapsulation of PTX in an amorphous state. In vitro drug release study demonstrated the redox-sensitivity of the micelles. In vitro and in vivo antitumor efficacy study indicated that the PTX-loaded mPEG-HA(DCA)-NAC micelles had excellent antitumor effect but with low toxicity to the body. It can be concluded that the mPEG-HA(DCA)-NAC micellar system represents a promising nanocarrier for delivery of PTX.