Biopolymer Induced Changes in Mucus Viscoelasticity

Marriott, Christopher; Beeson, Malcolm F.; Brown, David T.

doi:10.1007/978-1-4615-9254-9_9

Cited by 21 publications

(12 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It therefore appears that the velocity decreasing effect of the chitosans on turbinate MTR is predominantly physical, where the mucus and the chitosan interact probably predominantly by ionic interaction to form a viscous and adhesive complex. This supposition is in agreement with the results of Marriott et al 20 who found that adding biopolymers to mucus gels caused a thickening that increased with increasing molecular weight of the added biopolymer.…”

Section: Discussionsupporting

confidence: 87%

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

Aspden¹,

Mason²,

Jones³

et al. 1997

Journal of Pharmaceutical Sciences

237

105

View full text Add to dashboard Cite

In these studies, we examined the effect on mucociliary transport rates (MTR) of various 0.25% (w/v) chitosan solutions applied to human nasal tissue both ex vivo and in vivo. In the first study a range of chitosans with different molecular weights were applied to freshly amputated human nasal turbinates, and their effect on MTR was recorded. The transient inhibitory effect on turbinate MTR that was found for most of the chitosan preparations showed a marked dependence on the volume of chitosan solution applied and the molecular weight of the chitosan tested. The higher the molecular weight of the chitosan and the more chitosan applied, the longer the original MTR was depressed. A small scale human trial, investigating the effect of chitosan glutamate, on saccharin clearance times, was also undertaken. The study showed that a once daily application of a 0.25% solution of the chitosan for 7 days had no effect on either saccharin clearance times or nasal histology as examined by light microscopy.

show abstract

Section: Discussionsupporting

confidence: 87%

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

Aspden¹,

Mason²,

Jones³

et al. 1997

Journal of Pharmaceutical Sciences

237

105

View full text Add to dashboard Cite

show abstract

“…To investigate this possibility, we added human serum albumin (the most abundant protein in plasma [25]) to healthy sputum and measured elastic and viscous moduli over 24 hours. Albumin increased the elastic and viscous moduli immediately after addition to sputum (data not shown), a finding noted previously by others (26,27). However, albumin also prevented the usual declines in mucin cross-linking and length measured over 24 hours at 378C ( Figure 4D).…”

Section: Albumin Inhibits Protease-driven Mucus Degradationsupporting

confidence: 85%

Ex VivoSputum Analysis Reveals Impairment of Protease-dependent Mucus Degradation by Plasma Proteins in Acute Asthma

Innes¹,

Carrington²,

Thornton³

et al. 2009

Am J Respir Crit Care Med

109

104

View full text Add to dashboard Cite

Rationale: Airway mucus plugs, composed of mucin glycoproteins mixed with plasma proteins, are an important cause of airway obstruction in acute severe asthma, and they are poorly treated with current therapies. Objectives: To investigate mechanisms of airway mucus clearance in health and in acute severe asthma. Methods: We collected airway mucus from patients with asthma and nonasthmatic control subjects, using sputum induction or tracheal aspiration. We used rheological methods complemented by centrifugation-based mucin size profiling and immunoblotting to characterize the physical properties of the mucus gel, the size profiles of mucins, and the degradation products of albumin in airway mucus. Measurements and Main Results: Repeated ex vivo measures of size and entanglement of mucin polymers in airway mucus from nonasthmatic control subjects showed that the mucus gel is normally degraded by proteases and that albumin inhibits this degradation. In airway mucus collected from patients with asthma at various time points during acute asthma exacerbation, protease-driven mucus degradation was inhibited at the height of exacerbation but was restored during recovery. In immunoblots of human serum albumin digested by neutrophil elastase and in immunoblots of airway mucus, we found that albumin was a substrate of neutrophil elastase and that products of albumin degradation were abundant in airway mucus during acute asthma exacerbation. Conclusions: Rheological methods complemented by centrifugationbased mucin size profiling of airway mucins in health and acute asthma reveal that mucin degradation is inhibited in acute asthma, and that an excess of plasma proteins present in acute asthma inhibits the degradation of mucins in a protease-dependent manner. These findings identify a novel mechanism whereby plasma exudation may impair airway mucus clearance.

show abstract

“…Consequently, the mucus becomes thick and impaired clearance as well as bacterial growth characterize the lungs of patients with CF (8). The presence in CF sputa of components such as DNA, proteins, lipids and cations may influence the viscoelastic properties of the respiratory secretions (5,10,19). The pathologic CF mucus has led to the development of therapeutic medications intended to decrease its stiffness.…”

Section: Introductionmentioning

confidence: 99%

Impact of PEGylation on the mucolytic activity of recombinant human deoxyribonuclease I in cystic fibrosis sputum

et al. 2018

View full text Add to dashboard Cite

Highly viscous mucus and its impaired clearance characterize the lungs of patients with cystic fibrosis (CF). Pulmonary secretions of patients with CF display increased concentrations of high molecular weight components such as DNA and actin. Recombinant human deoxyribonuclease I (rhDNase) delivered by inhalation cleaves DNA filaments contained in respiratory secretions and thins them. However, rapid clearance of rhDNase from the lungs implies a daily administration and thereby a high therapy burden and a reduced patient compliance. A PEGylated version of rhDNase could sustain the presence of the protein within the lungs and reduce its administration frequency. Here, we evaluated the enzymatic activity of rhDNase conjugated to a two-arm 40 kDa polyethylene glycol (PEG40) in CF sputa. Rheology data indicated that both rhDNase and PEG40-rhDNase presented similar mucolytic activity in CF sputa, independently of the purulence of the sputum samples as well as of their DNA, actin and ions contents. The macroscopic appearance of the samples correlated with the DNA content of the sputa: the more purulent the sample, the higher the DNA concentration. Finally, quantification of the enzymes in CF sputa following rheology measurement suggests that PEGylation largely increases the stability of rhDNase in CF respiratory secretions, since 24-fold more PEG40-rhDNase than rhDNase was recovered from the samples. The present results are considered positive and provide support to the continuation of the research on a long acting version of rhDNase to treat CF lung disease.

show abstract

Biopolymer Induced Changes in Mucus Viscoelasticity

Cited by 21 publications

References 4 publications

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

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

Ex VivoSputum Analysis Reveals Impairment of Protease-dependent Mucus Degradation by Plasma Proteins in Acute Asthma

Impact of PEGylation on the mucolytic activity of recombinant human deoxyribonuclease I in cystic fibrosis sputum

Contact Info

Product

Resources

About