The rheology of nasal mucus: a review

Quraishi, M. S.; Jones, Nick; Mason, J. D. T.

doi:10.1046/j.1365-2273.1998.00172.x

Cited by 119 publications

(131 citation statements)

References 85 publications

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“…The mucin content, Ϸ1-3% by weight, is also similar among cervical, nasal, and lung mucus (50)(51)(52)(53)(54). The composition of water in the aforementioned mucus types all falls within the range of 90-98% (52,53,(55)(56)(57). The similar mucus composition and mucin glycoforms leads to similar rheology, characterized by log-linear shear thinning of viscosity.…”

Section: Discussionmentioning

confidence: 66%

“…In particular, the mucin glycoform MUC5B has been identified as the major secreted form of mucin in the mucosal layers protecting the CV tract (45,46), lungs (46,47), nose (48), and eye (49). The mucin content, Ϸ1-3% by weight, is also similar among cervical, nasal, and lung mucus (50)(51)(52)(53)(54). The composition of water in the aforementioned mucus types all falls within the range of 90-98% (52,53,(55)(56)(57).…”

Section: Discussionmentioning

confidence: 76%

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Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

Lai¹,

O’Hanlon

Harrold

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

904

1,012

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Nanoparticles larger than the reported mesh-pore size range (10 -200 nm) in mucus have been thought to be much too large to undergo rapid diffusional transport through mucus barriers. However, large nanoparticles are preferred for higher drug encapsulation efficiency and the ability to provide sustained delivery of a wider array of drugs. We used high-speed multiple-particle tracking to quantify transport rates of individual polymeric particles of various sizes and surface chemistries in samples of fresh human cervicovaginal mucus. Both the mucin concentration and viscoelastic properties of these cervicovaginal samples are similar to those in many other human mucus secretions. Unexpectedly, we found that large nanoparticles, 500 and 200 nm in diameter, if coated with polyethylene glycol, diffused through mucus with an effective diffusion coefficient (D eff) only 4-and 6-fold lower than that for the same particles in water (at time scale ‫؍‬ 1 s). In contrast, for smaller but otherwise identical 100-nm coated particles, D eff was 200-fold lower in mucus than in water. For uncoated particles 100 -500 nm in diameter, D eff was 2,400-to 40,000-fold lower in mucus than in water. Much larger fractions of the 100-nm particles were immobilized or otherwise hindered by mucus than the large 200-to 500-nm particles. Thus, in contrast to the prevailing belief, these results demonstrate that large nanoparticles, if properly coated, can rapidly penetrate physiological human mucus, and they offer the prospect that large nanoparticles can be used for mucosal drug delivery. drug delivery ͉ mucosal tissues ͉ particle tracking ͉ PEG

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 76%

Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

Lai¹,

O’Hanlon

Harrold

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

904

1,012

View full text Add to dashboard Cite

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“…The concentration of mucins in mucus gels typically ranges between 1-5% (1,(24)(25)(26)(27)(28). Based on these values, a cubic lattice model that assumes mucins to be long rigid polymers predicts an average pore size of 40-100 nm.…”

Section: Resultsmentioning

confidence: 99%

Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses

Lai

Wang²,

Hida³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

337

343

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The mechanisms by which mucus helps prevent viruses from infecting mucosal surfaces are not well understood. We engineered non-mucoadhesive nanoparticles of various sizes and used them as probes to determine the spacing between mucin fibers (pore sizes) in fresh undiluted human cervicovaginal mucus (CVM) obtained from volunteers with healthy vaginal microflora. We found that most pores in CVM have diameters significantly larger than human viruses (average pore size 340 ± 70 nm; range approximately 50–1800 nm). This mesh structure is substantially more open than the 15–100-nm spacing expected assuming mucus consists primarily of a random array of individual mucin fibers. Addition of a nonionic detergent to CVM caused the average pore size to decrease to 130 ± 50 nm. This suggests hydrophobic interactions between lipid-coated “naked” protein regions on mucins normally cause mucin fibers to self-condense and/or bundle with other fibers, creating mucin “cables” at least three times thicker than individual mucin fibers. Although the native mesh structure is not tight enough to trap most viruses, we found that herpes simplex virus (approximately 180 nm) was strongly trapped in CVM, moving at least 8,000-fold slower than non-mucoadhesive 200-nm nanoparticles. This work provides an accurate measurement of the pore structure of fresh, hydrated ex vivo CVM and demonstrates that mucoadhesion, rather than steric obstruction, may be a critical protective mechanism against a major sexually transmitted virus and perhaps other viruses.

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“…4 The mucus is a nonNewtonian fluid 5 that exhibits viscoelastic and shear thinning characteristics, and possesses a yield stress. 6,7 In the terminal bronchioles, beyond generation 17, there is essentially a single fluid layer whose viscous properties are similar to those of water.…”

Section: Introductionmentioning

confidence: 99%

The effect of viscoelasticity on the stability of a pulmonary airway liquid layer

2010

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The lungs consist of a network of bifurcating airways that are lined with a thin liquid film. This film is a bilayer consisting of a mucus layer on top of a periciliary fluid layer. Mucus is a non-Newtonian fluid possessing viscoelastic characteristics. Surface tension induces flows within the layer, which may cause the lung's airways to close due to liquid plug formation if the liquid film is sufficiently thick. The stability of the liquid layer is also influenced by the viscoelastic nature of the liquid, which is modeled using the Oldroyd-B constitutive equation or as a Jeffreys fluid. To examine the role of mucus alone, a single layer of a viscoelastic fluid is considered. A system of nonlinear evolution equations is derived using lubrication theory for the film thickness and the film flow rate. A uniform film is initially perturbed and a normal mode analysis is carried out that shows that the growth rate g for a viscoelastic layer is larger than for a Newtonian fluid with the same viscosity. Closure occurs if the minimum core radius, R min ͑t͒, reaches zero within one breath. Solutions of the nonlinear evolution equations reveal that R min normally decreases to zero faster with increasing relaxation time parameter, the Weissenberg number We. For small values of the dimensionless film thickness parameter , the closure time, t c , increases slightly with We, while for moderate values of , ranging from 14% to 18% of the tube radius, t c decreases rapidly with We provided the solvent viscosity is sufficiently small. Viscoelasticity was found to have little effect for Ͼ0.18, indicating the strong influence of surface tension. The film thickness parameter and the Weissenberg number We also have a significant effect on the maximum shear stress on tube wall, max͑ w ͒, and thus, potentially, an impact on cell damage. Max͑ w ͒ increases with for fixed We, and it decreases with increasing We for small We provided the solvent viscosity parameter is sufficiently small. For large Ϸ 0.2, there is no significant difference between the Newtonian flow case and the large We cases.

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The rheology of nasal mucus: a review

Cited by 119 publications

References 85 publications

Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses

The effect of viscoelasticity on the stability of a pulmonary airway liquid layer

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