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Purpose <p>Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and the second leading cause of cancer-related deaths, representing a major global health burden. The limitations and toxicity of conventional therapies have motivated extensive research into medicinal plants as alternative or complementary anticancer agents. Silymarin is recognized as a natural compound with significant anti-inflammatory and antioxidant properties. However, its clinical application is limited by poor solubility and low oral bioavailability. To address these challenges and enhance its therapeutic potential against CRC, this study focused on developing a nanoemulsion (NE) formulation of silymarin.</p> Methods <p>First, a silymarin-loaded NE was prepared using the spontaneous emulsification method, and the formulation that successfully passed the physical stability tests was selected for further studies. This formulation was evaluated in terms of particle size, morphology, surface potential, and antioxidant activity. In addition, its antiproliferative and apoptosis-inducing effects were assessed in the human colorectal carcinoma cell line HCT-116.</p> Results <p>Silymarin exhibited the highest solubility in fish oil, and an optimized NE containing 15&#xa0;mg/mL of silymarin was stable and transparent, whereas higher concentrations resulted in turbidity and instability. Thermodynamic stability tests confirmed its robustness under stress conditions. The selected NE displayed particle sizes below 20&#xa0;nm, spherical morphology, and favorable zeta potential values. Antioxidant assays demonstrated that silymarin-loaded NEs had significantly enhanced radical scavenging activity compared to free silymarin or unloaded NEs. In HCT-116 cells, silymarin-loaded NEs showed the strongest cytotoxic effect, with the lowest IC50, surpassing free silymarin and other controls. Apoptosis assays further confirmed that silymarin-loaded NEs induced markedly higher apoptotic cell death compared to the free compound.</p> Conclusion <p>These results indicate that silymarin-loaded NE is a promising delivery system capable of significantly enhancing the therapeutic efficacy of silymarin against CRC.</p>

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Nanoemulsion-Mediated Delivery of Silymarin to Boost Anticancer Potential against Colorectal Cancer

  • 期刊论文

  • 发表日期：

    2025年12月29日

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  • Shokoofeh Bahmani,
  • Shirin Shojaei,
  • Maryam Doostan,
  • Amir Kiani,
  • Roghayyeh Vakili-Ghartavol,
  • Hassan Maleki

摘要

Purpose

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and the second leading cause of cancer-related deaths, representing a major global health burden. The limitations and toxicity of conventional therapies have motivated extensive research into medicinal plants as alternative or complementary anticancer agents. Silymarin is recognized as a natural compound with significant anti-inflammatory and antioxidant properties. However, its clinical application is limited by poor solubility and low oral bioavailability. To address these challenges and enhance its therapeutic potential against CRC, this study focused on developing a nanoemulsion (NE) formulation of silymarin.

Methods

First, a silymarin-loaded NE was prepared using the spontaneous emulsification method, and the formulation that successfully passed the physical stability tests was selected for further studies. This formulation was evaluated in terms of particle size, morphology, surface potential, and antioxidant activity. In addition, its antiproliferative and apoptosis-inducing effects were assessed in the human colorectal carcinoma cell line HCT-116.

Results

Silymarin exhibited the highest solubility in fish oil, and an optimized NE containing 15 mg/mL of silymarin was stable and transparent, whereas higher concentrations resulted in turbidity and instability. Thermodynamic stability tests confirmed its robustness under stress conditions. The selected NE displayed particle sizes below 20 nm, spherical morphology, and favorable zeta potential values. Antioxidant assays demonstrated that silymarin-loaded NEs had significantly enhanced radical scavenging activity compared to free silymarin or unloaded NEs. In HCT-116 cells, silymarin-loaded NEs showed the strongest cytotoxic effect, with the lowest IC50, surpassing free silymarin and other controls. Apoptosis assays further confirmed that silymarin-loaded NEs induced markedly higher apoptotic cell death compared to the free compound.

Conclusion

These results indicate that silymarin-loaded NE is a promising delivery system capable of significantly enhancing the therapeutic efficacy of silymarin against CRC.