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

Mingchao Wang; Alessio Malfanti; Chiara Bastiancich; Véronique Préat

doi:10.1016/j.ijpx.2022.100147

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

Int J Pharm X. 2022 Dec 21:5:100147. doi: 10.1016/j.ijpx.2022.100147. eCollection 2023 Dec.

Authors

Mingchao Wang¹, Alessio Malfanti¹, Chiara Bastiancich^{1

2

3}, Véronique Préat¹

Affiliations

¹ Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Brussels, Belgium.
² Aix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol, Marseille, France.
³ Department of Drug Science and Technology, University of Turin, Turin, Italy.

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-TPGS_2000. 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: Combination therapy; Doxorubicin; Drug delivery; Glioblastoma; Micelles; α-Tocopherol succinate.