4.4 Article

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

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DOI: 10.1016/j.ijpx.2022.100147

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Glioblastoma; Micelles; alpha-Tocopherol succinate; Doxorubicin; Drug delivery; Combination therapy

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The study found that tocopherol succinate (TOS) and D-a-tocopherol polyethylene2000 succinate (TPGS2000) micelles could enhance the anti-cancer efficacy for the treatment of glioblastoma.
We hypothesized that tocopherol succinate (TOS) and D-a-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-TPGS(2000) micelles were formulated with synthesized DOXC12 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 DOXC12-TOSTPGS(2000) micelles by GL261 cells was observed. For cytotoxicity, DOXC12-TOS-TPGS(2000) micelles were evaluated on two glioblastoma cell lines and showed synergism between DOXC12 and TOS-TPGS(2000). The higher cytotoxicity of DOXC12-TOS-TPGS(2000 )micelles was mainly caused by necrosis. The DOXC12-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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