Synergistic effect of doxorubicin lauroyl hydrazone derivative delivered by α-tocopherol succinate micelles for the treatment of glioblastoma

Abstract

We hypothesized that tocopherol succinate (TOS) and D-α-tocopherol polyethylene2000 succinate (TPGS2000) micelles could work as a drug delivery system while enhancing the anti-cancer efficacy of doxorubicin lauryl hydrazone derivative (DOXC12) for the treatment of glioblastoma. The DOXC12-TOS-TPGS2000 micelles were formulated with synthesized DOXC12 and TPGS2000. They showed a high drug loading of hydrophobic DOXC12 (29%), a size of <100 nm and a pH sensitive drug release behaviour. In vitro, fast uptake of DOXC12-TOS-TPGS2000 micelles by GL261 cells was observed. For cytotoxicity, DOXC12-TOS-TPGS2000 micelles were evaluated on two glioblastoma cell lines and showed synergism between DOXC12 and TOS-TPGS2000. The higher cytotoxicity of DOXC12-TOS-TPGS2000 micelles was mainly caused by necrosis. The DOXC12-TOS-TPGS2000 micelles seem to be a promising delivery system for enhancing the anticancer efficacy of doxorubicin in glioblastoma (GBM).

Keywords

• Glioblastoma
• Micelles
• α-Tocopherol succinate
• Doxorubicin
• Drug delivery
• Combination therapy