Mucociliary clearance, respiratory tract

From a drug delivery perspective, the components of the host defence system comprise barriers that must be overcome to ensure efficient drug deposition as well as retention in and absorption from the respiratory tract. Important non-absorptive clearance mechanisms include mucociliary clearance, alveolar macrophages and metabolism (Figure 6.2). 

Aerosols must be respirable, that is, have a mean aerodynamic diameter of less than 5 xm, to ensure that a reasonable proportion will penetrate the respiratory tract defence systems of the nasal passages and the mucociliary clearance mechanisms. 

An impairment of the mucociliary clearance increases the susceptibility against respiratory infectious diseases frequently associated with marginal vitamin A deficiency (Sommer et ah, 1984). Interestingly vitamin A status following supplementation with 15-mg RP monthly for 2.5 months (Rahman et ah, 1996) was not improved in the presence of respiratory tract infections (Sommer et ah, 1986). 

Major determinants of the efficiency of mucociliary clearance are cilia density, periciliary fluid, and composition of mucus. Some drugs and excipients, such as preservatives in drug formulations, may diminish the ciliary movement in the nasal cavity and trachea. A suggested adverse effect of ciliostasis (permanently or momentarily arrest or impairment of ciliary activity) is lower respiratory tract infection as a result of impaired nasal microbiological defense. 

Batts, A.H. 1993. Mucociliary clearance and drug delivery via the respiratory tract. Adv Drug Deliv Rev 11 (3) 299. 

Inspired air, which is humidified and warmed in the nose, moves rapidly from the nasal cavity to the nasopharynx and into the trachea. Most airborne particles that are inspired are entrapped in the mucus layer of the respiratory region. Subsequently, these particles are removed from the nasal cavity to the nasopharynx and esophagus and eliminated via the gastrointestinal tract through a process known as mucociliary clearance. 

It is possible that systemic absorption of airborne aluminum occurs via the lungs, gastrointestinal tract after mucociliary clearance from the respiratory tract (ICRP 1994), or via the olfactory tract. Gitelman et al. (1995) found a better correlation between respirable aluminum air concentrations and urinary... 

In the respiratory tract, mucus is also involved in the process of mucociliary clearance, which contributes to the epithelial barrier properties by entrapping potentially hazardous substances, such as dust and microorganisms, within a viscoelastic mucus blanket. The mucus is then propelled by the claw-like tips of hair-like cilia towards the throat (movement occurs in a downwards direction from the nasal epithelium, or... 

The excretion of plutonium by humans approximately 30 years after occupational exposure to plutonium particles, primarily by inhalation, appeared to indicate that more plutonium was cleared in the urine than in the feces (Voelz et al. 1979). However, Leggett (1985) stated that at equilibrium, 4 times more plutonium was eliminated in the feces than in the urine. In laboratory animals, the primary route of excretion of plutonium was reportedly through the feces. From 10 to 35 times more plutonium was excreted in the feces than in the urine in dogs and rats (Bair and McClanahan 1961 Diel and Lundgren 1982 Sanders et al. 1976, 1977). In rats exposed by inhalation or intramuscular injection, greater amounts of plutonium have been found in the feces as soon as 8 days following inhalation exposure. This may be due to the removal of particles from the respiratory tract by the mucociliary elevator and the consequent swallowing of these particles or due to biliary clearance (Morin et al. 1972). 

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