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<p>Mucociliary clearance is the lung’s primary defense against inhaled pathogens and particulates, requiring optimal airway surface liquid hydration, mucus rheology, and coordinated ciliary beating. Diseases and pollutants disrupt these processes through altered ion transport, elevated pH and calcium, and goblet cell hyperplasia that leads to viscous mucus and airway obstruction. This process depends on chloride and bicarbonate secretion, nitric oxide–driven ciliary motility, and bronchodilation to maintain mucus fluidity and clearance. This study was conducted to determine if inhalable dry-powder formulations composed of natural pH-raising agents, calcium chelators, and supportive amino acids could be developed that was safe and rescued impaired mucociliary clearance. Inhalable powders produced by spray drying were developed and evaluated using <i>in vitro</i> studies in differentiated human airway cultures grown at an air–liquid interface before testing of formulations in an ovine model of impaired mucociliary clearance to determine efficacy and an inhalation toxicology study was conducted to evaluate safety of the final formulation. The powders demonstrated increased ciliary beat frequency, improved mucociliary clearance, preserved epithelial integrity, and minimal cytokine release <i>in vitro</i>, restored tracheal mucus velocity in a dose-dependent manner in sheep, and confirmed safety with an established a no observed adverse effect level of 2.32&#xa0;mg/kg/day that provides a 11.6-fold safety margin over a human dose of 50&#xa0;mg/day on a mg/g of lung weight basis. This scalable, inhaled formulation represents a novel strategy to support lung health by accelerating removal of inhaled microparticles and mitigating the respiratory impacts of worsening air pollution and climate change.</p> Graphical Abstract <p></p>

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Safety and Efficacy of Inhaled Natural Product Powders That Enhance Mucociliary Clearance

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月15日

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  • Dale J. Christensen,
  • Zachary Warnken,
  • Daria Stoltz,
  • Matthew Beerman,
  • Norman Amparado,
  • Michael Grass,
  • Nicholas Haft,
  • Juan Sabater

摘要

Mucociliary clearance is the lung’s primary defense against inhaled pathogens and particulates, requiring optimal airway surface liquid hydration, mucus rheology, and coordinated ciliary beating. Diseases and pollutants disrupt these processes through altered ion transport, elevated pH and calcium, and goblet cell hyperplasia that leads to viscous mucus and airway obstruction. This process depends on chloride and bicarbonate secretion, nitric oxide–driven ciliary motility, and bronchodilation to maintain mucus fluidity and clearance. This study was conducted to determine if inhalable dry-powder formulations composed of natural pH-raising agents, calcium chelators, and supportive amino acids could be developed that was safe and rescued impaired mucociliary clearance. Inhalable powders produced by spray drying were developed and evaluated using in vitro studies in differentiated human airway cultures grown at an air–liquid interface before testing of formulations in an ovine model of impaired mucociliary clearance to determine efficacy and an inhalation toxicology study was conducted to evaluate safety of the final formulation. The powders demonstrated increased ciliary beat frequency, improved mucociliary clearance, preserved epithelial integrity, and minimal cytokine release in vitro, restored tracheal mucus velocity in a dose-dependent manner in sheep, and confirmed safety with an established a no observed adverse effect level of 2.32 mg/kg/day that provides a 11.6-fold safety margin over a human dose of 50 mg/day on a mg/g of lung weight basis. This scalable, inhaled formulation represents a novel strategy to support lung health by accelerating removal of inhaled microparticles and mitigating the respiratory impacts of worsening air pollution and climate change.

Graphical Abstract