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Purpose <p>COVID-19 pandemic has driven the urgent need for effective antiviral treatments and strategies to combat its life-threatening complications. This study aims to develop a combination therapy approach using daclatasvir, as an antiviral agent, and xanthone, as a potent anti-inflammatory and antithrombotic compound, delivered via Bilosome-Chitosan Nanoparticles (BCNP).</p> Methods <p>The impact of varying the bilosome-to-chitosan ratio on the particle size (PS), zeta potential (ZP), and encapsulation efficiency (EE%) was evaluated. An optimized formula was prepared and tested for its antiviral activity and its potential for pulmonary protection in acute respiratory distress syndrome (ARDS) on mice model.</p> Results <p>The optimized formulation (O<sub>1</sub>) showed a PS of 222.67&#xa0;nm, a polydispersity index of 0.368, a ZP of -19.10 mV, and EE% of 83.78% for xanthone and 78.98% for daclatasvir. Controlled release profiles were attained, with daclatasvir released over 24&#xa0;h and xanthone sustained for up to 72&#xa0;h. The optimized formula showed promising deposition lung profile when tested using MPPD modelling. O<sub>1</sub> demonstrated strong antiviral activity against SARS-CoV-2, with a selectivity index (SI = 5.02) and an IC50 of 3.87 µM. Additionally, the formulation exhibited pulmonary protective effects by modulating the LncGAS5/ACE2 pathway, with significant improvements in the lungs of the mice model, offering a potential therapeutic strategy against ARDS, a severe and often fatal COVID-19 complication.</p> Conclusion <p>A successful BCNP formulation combining daclatasvir and xanthone was prepared, providing a promising combination therapy approach for COVID-19 treatment and ARDS prevention.</p>

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Combination Therapy Using Bilosome–Chitosan Nanocarriers for Effective Drug Delivery of Daclatasvir and Xanthone in COVID-19 and Acute Respiratory Distress Syndrome: A Preclinical Assessment

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月29日

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  • Marwa H. S. Dawoud,
  • Heba T. Elbalkiny,
  • Amr Abdelhamid,
  • Mai A. Amer,
  • Reham Wasfi,
  • Mai A. Zaafan

摘要

Purpose

COVID-19 pandemic has driven the urgent need for effective antiviral treatments and strategies to combat its life-threatening complications. This study aims to develop a combination therapy approach using daclatasvir, as an antiviral agent, and xanthone, as a potent anti-inflammatory and antithrombotic compound, delivered via Bilosome-Chitosan Nanoparticles (BCNP).

Methods

The impact of varying the bilosome-to-chitosan ratio on the particle size (PS), zeta potential (ZP), and encapsulation efficiency (EE%) was evaluated. An optimized formula was prepared and tested for its antiviral activity and its potential for pulmonary protection in acute respiratory distress syndrome (ARDS) on mice model.

Results

The optimized formulation (O1) showed a PS of 222.67 nm, a polydispersity index of 0.368, a ZP of -19.10 mV, and EE% of 83.78% for xanthone and 78.98% for daclatasvir. Controlled release profiles were attained, with daclatasvir released over 24 h and xanthone sustained for up to 72 h. The optimized formula showed promising deposition lung profile when tested using MPPD modelling. O1 demonstrated strong antiviral activity against SARS-CoV-2, with a selectivity index (SI = 5.02) and an IC50 of 3.87 µM. Additionally, the formulation exhibited pulmonary protective effects by modulating the LncGAS5/ACE2 pathway, with significant improvements in the lungs of the mice model, offering a potential therapeutic strategy against ARDS, a severe and often fatal COVID-19 complication.

Conclusion

A successful BCNP formulation combining daclatasvir and xanthone was prepared, providing a promising combination therapy approach for COVID-19 treatment and ARDS prevention.