In vitro and in vivo evaluation of redox-responsive sorafenib carrier nanomicelles synthesized from poly (acryic acid) -cystamine hydrochloride-D-α-tocopherol succinate

Abstract

In this study, a controlled drug release system based on redox-responsive nanomicelles for drug delivery was described. The system was constructed by linking poly (acryic acid) (PAA) with D-α-tocopherol succinate (VES) via a disulfide bond linker (ss). This amphiphilic polymer (PAAssVES) was synthesized by coupling reaction and its chemical structure was confirmed by FT-IR and ¹HNMR analyses. PAAssVES was found to self-assemble into nanomicelles with diameter of about 130 nm, and a critical micelle concentration of about 6.3 μg/mL. The Sorafenib-loaded nanomicelles (SFN-NM) were almost spherical as observed by transmission electron microscopy. Differential scanning calorimetry analysis showed that Sorafenib (SFN) was entrapped in the micelles in an amorphous or molecular state. The safety of SFN-NM was confirmed by hemolysis study. The release of SFN from the nanomicelles was dependent on the concentration of glutathione (GSH), with 85% of the drug being released under the maximum concentration (40 mM) of GSH used. SFN-NM exhibited stronger cytotoxicity than free SFN against BGC-823 cells under the same SFN concentration. Furthermore, pharmacokinetics study showed that the bioavailability of SFN in rat obtained by injecting the animal with SFN-NM was about 2.8-fold the bioavailability of SFN obtained by injecting the animal with free SFN. Thus, the redox-responsive SFN delivery system described in the current study could be considered as a carrier for delivering SFN.

Keywords:

• Sorafenib
• poly (acryic acid)
• D-α-tocopherol succinate
• redox responsive nanomicelles
• drug delivery

Acknowledgments

We thank Dr Alan K. Chang (Liaoning University) for valuable discussion and for his contribution to the writing of the manuscript.