Inhaled aerosol medications often do not distribute evenly within diseased lungs leaving some poorly ventilated regions untreated.  Surface tension driven flows may be useful for dispersing medications over the internal surfaces of the lungs after inhalation and aerosol deposition, increasing the portion of the lung reached by the treatment.  Surface conditions within the lung are complex with glycoprotein mucus overlying a thin, watery periciliary layer.   Endogenous lipid and protein surfactants are present but their concentrations vary by location and are difficult to assess.   We have utilized a series of model substrates to test surfactant-based liquid and powder formulations delivered with and without aerosolization.  Surfactant formulations demonstrate improved drug spreading and up to multi-fold increases in treated area with small molecule, nano-, and micrometer sized drug analogs.  Important formulation parameters affecting spread area include the surface tension gradient between the formulation and the airway surface and surfactant inventory at the deposition site.  Lipid surfactants, similar to those found naturally in the lung, can be used successfully if surfactant aggregates in the solutions are successfully dispersed through aerosolization or other means.  We have demonstrated the presence of a surfactant spreading front that precedes formulation spreading and causes rapid and significant changes in surface tension at a distance from the deposition site.  With a liquid aerosol, the escape of surfactant from individual droplets results in significant droplet field spreading after aerosol deposition.  Surfactant and drug powder blends also demonstrate substantial dispersion.  Challenges to further formulation development include the varying and poorly characterized surface conditions within the lung, the complex and vast architecture of the airways and airspaces, and the need for safe formulations with very low surface tensions.  Successful development of self-dispersing formulations could significantly improve treatments for diseases such as cystic fibrosis.<br/>

Surfactant additives to improve the distribution of inhaled drugs in the lungs

251st National Meeting (2016)

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