A Repurposed Drug for Brain Cancer: Enhanced Atovaquone Amorphous Solid Dispersion by Combining a Spontaneously...

Area of Science:

• Neuro-oncology
• Pharmaceutical Sciences
• Drug Delivery

Background:

• Glioblastoma multiforme (GBM) is a highly lethal brain tumor.
• Atovaquone inhibits signal transducer and activator of transcription 3 (STAT3), a potential GBM therapeutic target.
• Current atovaquone formulations fail to reach effective brain concentrations for GBM treatment.

Purpose of the Study:

• To evaluate atovaquone's efficacy against GBM.
• To develop an improved oral formulation of atovaquone for enhanced brain delivery.
• To achieve therapeutic drug levels in the brain for GBM therapy.

Main Methods:

• Atovaquone was formulated as an amorphous solid dispersion using a polymer and a spontaneously emulsifying component (SEC).
• The formulation's properties (wetting, disintegration, dispersibility, dissolution) were optimized.
• In vitro cytotoxicity assays against GBM cell lines and in vivo pharmacokinetic studies were performed.

Main Results:

• The amorphous solid dispersion significantly improved atovaquone's formulation properties.
• Atovaquone demonstrated cytotoxicity against GBM cell lines in vitro.
• In vitro studies confirmed the potential for achieving target atovaquone brain concentrations.
• A proof-of-concept in vivo study supported enhanced brain exposure.

Conclusions:

• The developed amorphous solid dispersion formulation is effective in improving atovaquone's oral bioavailability.
• This novel formulation holds promise for delivering therapeutically effective brain concentrations of atovaquone for GBM treatment.
• Further investigation into this formulation for clinical application in GBM is warranted.