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

The antineoplastic activity of the thioredoxin reductase 1 (TrxR) inhibitor, auranofin (AF), has already been investigated in various cancer mouse models as a single drug, or in combination with other molecules. However, there are inconsistencies in the literature on the solvent, dose and administration route of AF treatment in vivo. Therefore, we investigated the solvent and administration route of AF in a syngeneic SB28 glioblastoma (GBM) C57BL/6J and a 344SQ non-small cell lung cancer 129S2/SvPasCrl (129) mouse model. Compared to daily intraperitoneal injections and subcutaneous delivery of AF via osmotic minipumps, oral gavage for 14 days was the most suitable administration route for high doses of AF (10-15 mg/kg) in both mouse models, showing no measurable weight loss or signs of toxicity. A solvent comprising 50% DMSO, 40% PEG300 and 10% ethanol improved the solubility of AF for oral administration in mice. In addition, we confirmed that AF was a potent TrxR inhibitor in SB28 GBM tumors at high doses. Taken together, our results and results in the literature indicate the therapeutic value of AF in several in vivo cancer models, and provide relevant information about AF's optimal administration route and solvent in two syngeneic cancer mouse models.

 

Comments：

It's important to optimize the administration route and solvent of drugs in animal models to ensure their efficacy and safety before moving on to clinical trials. Auranofin's antineoplastic activity as a TrxR inhibitor has shown promise in various cancer mouse models, and your study's findings on the optimal administration route and solvent could contribute to its further development as a cancer therapy. It's also good to hear that high doses of AF did not result in weight loss or signs of toxicity, suggesting that it may have a favorable safety profile at these doses. Overall, your study provides valuable information for researchers studying AF's potential as a cancer therapy.

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S6704 PEG300 PEG300 (Polyethylene glycol 300) is a water-miscible polyether widely used in biochemistry, structural biology, and medicine in addition to pharmaceutical and chemical industries. It serves as a kind of solubilizer, excipient, lubricant, and chemical reagent. PEG300 helps in the formation of hydrogels in situ upon mixing with silk. These PEG–silk hydrogels are of interest for many biomedical applications, such as anti-fouling and anti-adhesion.

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