Development of D-Limonene Nanoemulsions for Oral Cancer Inhibition: Investigating the Role of Ostwald Ripening

Suwisit Manmuan1, Yotsanan Weerapol1, Tiraniti Chuenbarn1

  • 1Faculty of Pharmaceutical Sciences, Burapha University, Chon Buri 20131, Thailand.

Insights

D-limonene (D-LMN) nanoemulsions, stabilized with inhibitors like perilla oil, show significant potential against oral cancer. These nanoemulsions effectively reduce cancer cell viability, metastasis, and invasion, offering a promising therapeutic avenue.

Area of Science:

  • Nanotechnology
  • Cancer Research
  • Pharmacology

Background:

  • D-limonene (D-LMN) is a natural compound with potential anti-cancer properties.
  • Nanoemulsions offer improved delivery and efficacy of therapeutic agents.
  • Oral cancer remains a significant global health challenge requiring novel treatment strategies.

Purpose of the Study:

  • To investigate the impact of Ostwald ripening inhibitors on D-limonene (D-LMN) nanoemulsions.
  • To evaluate the anti-cancer effects of D-LMN nanoemulsions on oral cancer cells.
  • To determine the optimal formulation of D-LMN nanoemulsions using various inhibitors.

Main Methods:

  • Formulation of D-LMN nanoemulsions with different inhibitors (olive oil, soybean oil, perilla oil) at varying ratios.
  • Characterization of nanoemulsions including droplet size, zeta potential, and stability.
  • In vitro evaluation of cytotoxicity, anti-metastatic, anti-invasive, apoptosis induction, and cell cycle arrest in oral cancer cells.

Main Results:

  • The 75:25 D-LMN to inhibitor ratio yielded the smallest droplet size and highest stability, especially with perilla oil.
  • D-LMN nanoemulsions significantly reduced oral cancer cell viability, metastasis, and invasion.
  • Apoptosis was induced via modulation of BAX, BCL-XL, Cytochrome c, and Caspase-9.
  • Cell cycle arrest was observed through downregulation of Cyclin D1, CDK2, CDK4, and CDK6.

Conclusions:

  • D-limonene (D-LMN) nanoemulsions formulated with Ostwald ripening inhibitors demonstrate potent anti-oral cancer activity.
  • Perilla oil is an effective inhibitor for creating stable and effective D-LMN nanoemulsions.
  • These findings suggest D-LMN nanoemulsions are a promising alternative therapeutic strategy for oral cancer treatment.

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