Oral solid self-emulsifying system containing non oncology drug combination for repurposing in melanoma treatment: In vitro cytotoxicity, and in vivo hematotoxicity and pharmacokinetic study

Year 2025, Volume: 29 Issue: 4, 1495 - 1506, 05.07.2025

Rameshwar Ardad Shashikant Dhawale , Arehalli Manjappa Sunil T. Galatage Ahmad Salawi

https://doi.org/10.12991/jrespharm.1734556

Abstract

The goal of the current research was to identify a safe and effective non-oncology drug combination as a substitute to existing toxic chemotherapeutics for the treatment melanoma. Further intend was to develop an oral solid self-emulsifying drug delivery system (S-SEDDS) for concurrent delivery of identified combination. The drug containing S-SEDDS was prepared and characterized for flowability, compressibility, drug content, particle size and zeta potential, and in vitro cytotoxicity against melanoma cells. In silico molecular docking for drug with excipients interaction shows compatibility with each other. Moreover, the formulations were characterized in vivo for hepatotoxicity and pharmacokinetic study in rats. The S-SEDDS showed good flowability and compressibility. The particle size of S-SEDDS upon dilution was found in nanometer range. Furthermore, the in vitro cytotoxicity of S-SEDDS containing non-oncology drug (NOD) combination [ketoconazole (KCZ), tadalafil (TLF), disulfiram (DSR)] and docetaxel (DTX) was observed to be higher than S-SEDDS containing only NOD combination against mouse melanoma cells. No significant change in the hematological parameters, animal vital organs weights, and body weights were observed after oral administration of S SEDDS containing non-oncology drug combination with DTX indicating their safety. In addition, significant (p< 0.05) improvement in the oral bioavailability of DTX was observed following its administration in the form of S-SEDDS when compared to the Taxotere in the rats. The developed S-SEDDS containing non-oncology drug combination alone and in combination with docetaxel could be a promising and safe approach in the effective treatment of melanoma.

Keywords

Repurposing , melanoma , self-emulsifying drug delivery , cytotoxicity , acute toxicity , pharmacokinetics

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