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Objective <p>Lung cancer chemoprevention modalities are gaining wide attention as it is the second most diagnosed cancer type and the leading cause of cancer-related deaths. Our previous studies reported unique lung cancer chemoprevention capability with a repurposed drug combination of sulfasalazine (SAS) and disulfiram (DSF). However, their efficacy is limited by poor bioavailability. To overcome this challenge, we developed bioenhanced oil-in-water (o/w) nano self-emulsifying drug delivery system (Nano-SEDDS) formulations of SAS and DSF.</p> Methods <p>Unique isotropic Nano-SEDDS of SAS and DSF were developed and optimized using a single-step mix method followed by <i>in vitro</i> physicochemical characterization and stability studies<i>.</i> An <i>in vivo</i> pharmacokinetic and tissue-biodistribution study was undertaken to test the proposed hypothesis of bioavailability enhancement with Nano-SEDDS of SAS and DSF.</p> Results <p>The optimal Nano-SEDDS formulation exhibited low nanodroplet sizes (&lt; 200&#xa0;nm), high drug content, and 4.5-fold (<i>p</i> &lt; 0.01) and 3.75-fold (<i>p</i> &lt; 0.01) enhancement in <i>in vitro</i> dissolution of SAS and DSF compared to the respective free drugs. The Nano-SEDDS formulations were also confirmed to be stable at room temperature in compliance with ICH guidelines. Further, SAS Nano-SEDDS showed a dose-dependent increment in oral bioavailability as shown by a significant 7.9-fold (<i>p</i> &lt; 0.0001) enhancement in dose-normalized AUC at a dose of 10&#xa0;mg/kg compared to free drug treatment at a control dose of 250&#xa0;mg/kg.</p> Conclusion <p>Overall, the studies corroborated the successful formulation of bioavailability-enhanced SAS and DSF Nano-SEDDS with future co-delivery applications for lung cancer prevention.</p> Graphical Abstract <p></p>

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Development, Optimization, and Evaluation of Nano Self-Emulsifying Drug Delivery System Formulation Platform for Oral Bioavailability Enhancement of Sulfasalazine and Disulfiram in Lung Cancer Chemoprevention

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月16日

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  • Preshita Desai,
  • Katherine Bang,
  • Mohammed Riaz Hasan Chowdhury,
  • Zhijun Kevin Wang,
  • Jeffrey Wang,
  • Sunil Prabhu,
  • Xueqing Liang,
  • Fekadu Kassie

摘要

Objective

Lung cancer chemoprevention modalities are gaining wide attention as it is the second most diagnosed cancer type and the leading cause of cancer-related deaths. Our previous studies reported unique lung cancer chemoprevention capability with a repurposed drug combination of sulfasalazine (SAS) and disulfiram (DSF). However, their efficacy is limited by poor bioavailability. To overcome this challenge, we developed bioenhanced oil-in-water (o/w) nano self-emulsifying drug delivery system (Nano-SEDDS) formulations of SAS and DSF.

Methods

Unique isotropic Nano-SEDDS of SAS and DSF were developed and optimized using a single-step mix method followed by in vitro physicochemical characterization and stability studies. An in vivo pharmacokinetic and tissue-biodistribution study was undertaken to test the proposed hypothesis of bioavailability enhancement with Nano-SEDDS of SAS and DSF.

Results

The optimal Nano-SEDDS formulation exhibited low nanodroplet sizes (< 200 nm), high drug content, and 4.5-fold (p < 0.01) and 3.75-fold (p < 0.01) enhancement in in vitro dissolution of SAS and DSF compared to the respective free drugs. The Nano-SEDDS formulations were also confirmed to be stable at room temperature in compliance with ICH guidelines. Further, SAS Nano-SEDDS showed a dose-dependent increment in oral bioavailability as shown by a significant 7.9-fold (p < 0.0001) enhancement in dose-normalized AUC at a dose of 10 mg/kg compared to free drug treatment at a control dose of 250 mg/kg.

Conclusion

Overall, the studies corroborated the successful formulation of bioavailability-enhanced SAS and DSF Nano-SEDDS with future co-delivery applications for lung cancer prevention.

Graphical Abstract