Optimization of the Solvent and In Vivo Administration Route of Auranofin in a Syngeneic Non-Small Cell Lung Cancer...

Area of Science:

• Oncology
• Pharmacology
• Drug Delivery

Background:

• Auranofin (AF) is a thioredoxin reductase 1 (TrxR) inhibitor with demonstrated antineoplastic activity.
• Existing literature presents inconsistencies regarding optimal in vivo administration parameters for AF.
• Establishing reliable administration methods is crucial for further clinical translation of AF in cancer therapy.

Purpose of the Study:

• To determine the optimal solvent and administration route for auranofin (AF) in preclinical cancer models.
• To evaluate the efficacy and safety of AF at high doses using different administration strategies.
• To confirm the inhibitory activity of AF on TrxR in glioblastoma tumors.

Main Methods:

• Investigated oral gavage, intraperitoneal injections, and subcutaneous delivery of AF in SB28 glioblastoma and 344SQ non-small cell lung cancer mouse models.
• Tested a novel solvent mixture (50% DMSO, 40% PEG300, 10% ethanol) to enhance AF solubility for oral administration.
• Assessed AF's impact on tumor TrxR inhibition and monitored mouse weight and signs of toxicity.

Main Results:

• Oral gavage over 14 days proved to be the most suitable administration route for high-dose AF (10-15 mg/kg) in both cancer models.
• The developed solvent significantly improved AF solubility for oral delivery, with no observable toxicity or weight loss in mice.
• High-dose AF effectively inhibited TrxR in SB28 glioblastoma tumors, confirming its potent biological activity.

Conclusions:

• Oral gavage represents an optimal and safe administration route for high-dose auranofin in preclinical cancer models.
• A specific solvent formulation enhances AF solubility and tolerability for oral administration.
• These findings support the therapeutic potential of AF in vivo and provide critical guidance for future drug development and clinical studies.