Mucociliary transport rate

New techniques have been developed for the direct measurement of mucociliary transport rates in the trachea. Yeates et al. used an external gamma camera to follow a bolus of labeled microspheres deposited in the large airways by aerosol inhalation they fitted a log-normal distri-... 

Pritchard K., et al., Evaluation of the bioadhesive properties of hyaluronan derivatives detachment weight and mucociliary transport rate studies, J. Pharm., 129, 137, 1996. 

It is possible to study cilia beat frequency and drug interaction with mucus independently using models such as tissue explants or cultures of ciliated cells or purified mucus preparations. However, these are not able to provide information about mucociliary transport rates. For such studies, a model incorporating the integrated cilia and mucus components is required such as the frog palate. Drugs, preservatives and absorption enhancers, and bioadhesive formulations have been extensively studied in this model [9]. 

Pritchard, K., Lansely, A. B., Martin, G. P., Helliwell, M., Marriott, C., and Benedetti, L. M. (1996), Evaluation of bioadhesive properties of hyaluronan derivatives, detachment weight and mucociliary transport rate studies, Int. J. Pharm., 129,137-145. 

Aspden, T.J. Mason, J.D. Jones, N.S. Lowe, J. Skaugrud, O. Ilium, L. Chitosan as a nasal delivery system the effect of chitosan solutions on in vitro and in vivo mucociliary transport rates in human turbinates and volunteers. J. Pharm. Sci. 1997, 86 (4), 509-513. 

How long does the drug remain in the lung (dissolution rate, mucociliary transport rate, rates of cellular entrapment) ... 

Clearance in the upper, or ciliated, region is governed by the rate of mucus transport along the airways. These rates have been measured in the human nose and in dogs, rats, and other species. Asmundsson and Kilbum, Hilding, and Iravani established that mucociliary clearance rates increase from the distal bronchi toward the trachea. Because bronchial openings retard mucus flow, bifurcations receive an accumulation of mucus and associated particles. The rate of mucus production and mucus thickness and velocity vary from one person to another. Thickness increases and velocity decreases greatly when some toxic elements are present in the airway. 

Mucociliary clearance can be studied in vivo in humans using gamma scintigraphy to follow the clearance of radiolabeled solutions from the nasal cavity or by measuring the transport rate of radiolabeled markers administered to the nasal epithelium. Simpler methods are used to monitor the appearance of a strongly colored dye (by visual inspection) or sweet tasting substance such as saccharin (by taste) at the pharyngeal cavity. 

Figure 9 Effect of pulmonary dissolution rate on pulmonary selectivity. The dose of 300 p,g was allowed to dissolve immediately (A), with a half-life of 3 hr (B), or with a half-life of 24 hr (C). Pulmonary selectivity [area between pulmonary (upper line) and systemic (lower line) receptor occupancies] observed in A-C are summarized in D. The dose was given once a day at steady state. A slower release/dissolution of the drug in the lung does significantly increase pulmonary selectivity however, very slow dissolution rates further decrease pulmonary selectivity as the undissolved drug particles are removed from the lung by the mucociliary transport system.

Changes in the viscoelasticity of mucus gels alter the mucus clearance rate and, hence, particle transport efficiency. An increase in viscosity [148], or a decrease in elasticity [132,149] of mucus gels leads to slower mucociliary clearance rates, allowing particles a longer time to penetrate mucus. 

Wagner HN Jr (1995) Regional ventilation and perfusion. In Wagner HN Jr, Szabo S, Buchanan JW (eds) Principles of nuclear medicine, 2nd edn. Saunders, Philadelphia, pp 887-895 Wanner A (1977) Clinical aspects of mucociliary transport. Amer Rev Respir Dis 116 73-125 Wassner SJ (1981) Assessment of glomerular filtration rate using single injection of technetium Tc-99m pentetate. Am J Dis Child 135 374-375... 

Mucociliary transport, the primary form of particulate clearance in the ppper respiratory tract, moves particles to the nasopharynx at rates of 7 mmftnin in the nose and tra-ch and 1 mm/min in the upper bronchial tree. 

The relation between the viscosity and elasticity of the secretions is one of the determining factors in transport velocity. If the gel phase is in practice the only one really transported, the sol phase creates a low-resistance milieu where the cilia can beat, an environment that is essential for transport in the direction of the upper airways. One of the most important rheological properties of mucus is viscosity. Viscosity is resistance to flow and represents the capacity of a material to absorb energy while it moves. Elasticity is the capacity to store the energy used to move or deform material. The ratio between viscosity and elasticity appears to be an important determinant of the transport rate (6,10). Mucus transport by ciliary beating is influenced by the viscoelastic and surface properties of the mucus. Theoretical models suggest that a decrease in the ratio of viscosity to elasticity can result in an increase in mucociliary transport (13). 

Yeates DB, Aspin N, Levison H, Jones MT, Bryan A. Mucociliary tracheal transport rates in man. J Appl Physiol 1975 39 487-495. 

Impairment of mucociliary clearance, the rate at which mucus is transported from the nose to the pharynx, was found in a study of 68 Danish hardwood furniture workers. Mucostasis (defined as a nasal transit time of 40 or more minutes) increased in direct proportion to the dust concentration at 25.5mg/m, 63% had mucostasis vs. 11% at 2.2 mg/m. ... 

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