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

authors

• Wang Mingchao
• Malfanti Alessio
• Bastiancich Chiara
• Préat Véronique

keywords

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

document type

abstract

We hypothesized that tocopherol succinate (TOS) and D-α-tocopherol polyethylene2000 succinate (TPGS$_{2000}$) micelles could work as a drug delivery system while enhancing the anti-cancer efficacy of doxorubicin lauryl hydrazone derivative (DOXC$_{12}$) for the treatment of glioblastoma. The DOXC$_{12}$-TOS-TPGS$_{2000}$ micelles were formulated with synthesized DOXC$_{12}$ and TPGS$_{2000}$. 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 DOXC$_{12}$-TOS-TPGS$_{2000}$ micelles by GL261 cells was observed. For cytotoxicity, DOXC$_{12}$-TOS-TPGS$_{2000}$ micelles were evaluated on two glioblastoma cell lines and showed synergism between DOXC$_{12}$ and TOS-TPGS2000. The higher cytotoxicity of DOXC$_{12}$-TOS-TPGS$_{2000}$ micelles was mainly caused by necrosis. The DOXC$_{12}$-TOS-TPGS$_{2000}$ micelles seem to be a promising delivery system for enhancing the anticancer efficacy of doxorubicin in glioblastoma (GBM).

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