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<p>Therapeutic deep eutectic solvents (THEDES) are a subset of DESs, where active pharmaceutical ingredients (APIs) are incorporated, to use DESs as drug delivery vehicles. Ursolic acid (UA) is a bioactive natural triterpenoid with a broad spectrum of pharmacological activities and potential applications in medicine and nutrition. Five Novel THEDES were synthesized for the first time using Ursolic acid as hydrogen bond donor (HBD) and long chain fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid and oleic acid were used as hydrogen bond acceptors (HBA). The in vitro antimicrobial screening revealed that UA- Lauric acid(ULA) THEDES exhibit high antibacterial effect against MRSA than other long chain fatty acids. Box-Behnken- response surface methodology (RSM) experimental design was developed having transcutol as solvent to increase the solubility of the synthesized THEDES and the optimum conditions were observed to be UA -1.0760&#xa0;m.mol, Lauric acid – 2.028&#xa0;m.mol, Transcutol – 2.0010&#xa0;m.mol for the maximum inhibition of MRSA. The treatment group in the in vivo zebrafish infection model exhibited &gt; 2.1fold reduction in colony count on ULT THEDES administration. Toxicity assessments indicated no significant changes in liver and brain enzyme levels. Liver morphology images revealed no severe cytological changes after ULT THEDES treatment.</p>

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Ursolic Acid-fatty Acid Based Therapeutic Deep Eutectic Solvents: Response Surface Methodology Based Optimization and in vivo anti-microbial Effects against MRSA

  • 期刊论文

  • 发表日期：

    2026年2月24日

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  • Ramya M. Subramani,
  • Saisubramanian Nagarajan,
  • Arvind Sivasubramanian

摘要

Therapeutic deep eutectic solvents (THEDES) are a subset of DESs, where active pharmaceutical ingredients (APIs) are incorporated, to use DESs as drug delivery vehicles. Ursolic acid (UA) is a bioactive natural triterpenoid with a broad spectrum of pharmacological activities and potential applications in medicine and nutrition. Five Novel THEDES were synthesized for the first time using Ursolic acid as hydrogen bond donor (HBD) and long chain fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid and oleic acid were used as hydrogen bond acceptors (HBA). The in vitro antimicrobial screening revealed that UA- Lauric acid(ULA) THEDES exhibit high antibacterial effect against MRSA than other long chain fatty acids. Box-Behnken- response surface methodology (RSM) experimental design was developed having transcutol as solvent to increase the solubility of the synthesized THEDES and the optimum conditions were observed to be UA -1.0760 m.mol, Lauric acid – 2.028 m.mol, Transcutol – 2.0010 m.mol for the maximum inhibition of MRSA. The treatment group in the in vivo zebrafish infection model exhibited > 2.1fold reduction in colony count on ULT THEDES administration. Toxicity assessments indicated no significant changes in liver and brain enzyme levels. Liver morphology images revealed no severe cytological changes after ULT THEDES treatment.