Effects of Mucus Degrading Agents on Particle Transport

The prolonged retention of viscous airway secretions in the diseased lung (e.g., CF and COPD) can lead to recurring bacterial infections, resulting in a viscous, more purulent sputum [155]. Increased mucus viscoelasticity may be attributed to extensive disulphide and lectin bonding, poor hydration, and/or excess concentrations of extracellular DNA or actin [155]. In these situations, therapeutics have been used to reduce the viscosity of airway secretions to improve the rate of mucociliary clearance.

Mucolytic agents, such as N-acetylcysteine [88], guaifenesin [156], and diothiothreitol (DTT) [157], are used clinically and/or in vitro to reduce mucus viscosity. Lytic agents, such as recombinant human deoxynuclease I (rhDNase I, or Pulmozyme®) and Gelsolin® have also been effective in clearing viscous

Figure 5 Fluorescent image of 200-nm carboxylated polystyrene microspheres in CF mucus collected by expectoration from an 18-year-old Caucasian male. Mucus fibers are bundled together, forming a thick mucus cord, which can be visualized owing, in part, to the adhesion of fluorescent microspheres.

airway secretions [155]. Pulmozyme® enzymatically degrades extracellular DNA in human sputum [139]. Gelsolin® severs noncovalent bonds between polymerized monomers of actin filaments. Gelsolin® may scavenge actin filaments released during the inflammation process, increasing the effectiveness of DNase I [158]. Finally, the application of pulmonary surfactant to canine airways increased the mucus transport velocity nearly 400% in one study [147]. The affect of using mucus-altering agents as adjuncts in gene delivery was investigated: the addition of mucus-altering agents produced similar transgene expression to mechanical mucus depletion [88].

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