Viscosity of the mucus

Expectorants increase the production of respiratory secretions, which in turn appears to decrease the viscosity of the mucus. This helps to raise secretions from the respiratory passages. An example of an expectorant is guaifenesin. 

Patients suffering from cystic fibrosis often use various aerosolized drugs. To reduce the viscosity of the mucus in the airways, recombinant human deoxyribonuclease is used. This enzyme is the first recombinant protein that has been developed for specific delivery to the lungs via the airways. It has a local action on the mucus in the airways and its absorption is minimal. Another drug that decreases the viscosity of the mucus is acetylcysteine. Aerosolized antibiotics are a further group of therapeutics that is widely used by cystic fibrosis patients. Solutions of antibiotics like tobramycin or colistin are used in nebulizers to prevent exacerbation of the disease. Pentamidine has been used for the prophylaxis of Pneumocystis pneumonia in patients infected with HIV virus, while chronic rejection of lung transplants provided a reason to develop an aerosol formulation of cyclosporine A. 

Absorption can be enhanced via several mechanisms. These include increased membrane fluidity, chelation of the calcium ions that serve to maintain the dimension of the intercellular space, solubilization of the mucosal membrane, enhancement in water flux, and reduction of the viscosity of the mucus layer adhering to the epithelial cells. A discussion of various types of pentration enhancers and their mechanism (s) of action is given in Chapter 8 (Section 8.7.1). Table 6.4 summarises the oral absorption enhancers that have been tested for oral dmg delivery. 

Penetration enhancers are often used to improve peptide bioavailability in nasal formulations. A variety of different enhancers have been tried, and they work by one or several combined mechanisms. Some act by increasing the membrane fluidity and reducing the viscosity of the mucus layer, thereby increasing membrane permeability. Others act by transient loosening of the tight junctions between epithelial cells. The types of penetration enhancers discussed in the research literature include the following. 

A well operating ciliary epithelium is important in prevention as well as cure of many diseases of the airways. The activity of the cilia depends on a number of factors, including temperature and humidity of the air, pH and viscosity of the mucus layer. Besides pathological conditions (allergic diseases, sinusitis, measles) also chemical influence may inhibit the action or even destroy the ciliary epithelium. This is called ciHotoxicity. CUiotoxicity is an important reason to restrict the period of use of nasal preparations. 

Professor D Dowson (Institute of Tribology, School of Mechanical Engineering, University of Leeds, Leeds, UK). The viscosity of the mucus appears to fall to about 40 or 50 mPa.s at shear rates of only a few hundred reciprocal seconds. Were you able to estimate the shear rate during locomotion ... 

Reply bv the Authors The locomotion of a snail is done by pedal waves of the ventral surface. Therefore, the part of the ventral surface in which the pedal wave does not pass through contacts to the ground without slip namely statically. Consequently, the mucus sandwiched between that part of the ventral surface and the ground is also in a static state. As a result, it is considered that the viscosity of the mucus of the contact part of the ventral surface has the value of the shear rate of 0 1 /s in Fig.2. 

The efficiency of mucociliary transport depends on the force of kinociUary motion and the viscosity of bronchial mucus. Both factors can be altered pathologically (e.g., in smoker s cough, bronchitis) or can be adversely affected by drugs (atropine, antihistamines). 

Many physiological aspects affect drug absorption from the rectum (Table 7.1). Influential factors include the pH of the rectal contents, state of the mucus layer, volume and viscosity of rectal fluid, luminal pressure from the rectal wall on the dosage form, enzymatic and microbacterial degradation by rectal epithelium, presence of stools, and venous drainage differences within the rectosigmoid regions. 

As noted in Section HE, both layers decrease the absorption rate, especially of large water-soluble molecules, since the diffusion coefficient is directly proportional to the reciprocal values of both the hydrodynamic radius and the viscosity of the layers. About the influence of absorption enhancers on mucus rheology very little is known. Bib salts and phospholipids are known to reduce the viscoelasticity of bronchial mucus aid probably also of mucus layers in the gastxointestinal tract [40. Hie results should be interpreted with caution since it is not the observed macro )viscosity that determines the diffusion rate in polymer... 

Mucus serves as a lubricant and protective layer. Its most important property is its viscoelasticity, which enables it to act as a mechanical barrier, but also allows it to flow. The presence of a mucus layer has important implications for drag delivery. Mucus acts as a physical barrier through which drug molecules must diffuse, prior to reaching the absorbing surface. The rate of diffusion through the mucus will be dependent upon such factors as the thickness of the mucus layer, mucus viscosity and any interactions which may occur between the drag and mucus. 

Fig. 9. Treatment of gastric and colonic mucus with lysozyme. Effect of lysozyme in human tears on viscosity of gastric mucus. To three samples of this preparation, 2 ml each, were added, respectively 0.5 ml distilled water, 0.5 ml solution containing 5 mg crystallized pepsin, and 0.5 ml 50% solution of human tears in water. Incubation at pH 6.5 and 37° C. The mucoproteose content was determined after 24 hours of incubation. From Glass et al. (G50).

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