Mucus mucociliary clearance

Barriers to pulmonary absorption of proteins and peptides include respiratory mucus, mucociliary clearance, pulmonary enzymes/proteases, alveolar lining layer, alveolar epithelium, basement membrane, macrophages and other cells [3, 18]. The molecular weight cutoff of tight junctions for alveolar type I cells is 0.6 nm, while endothelial junctions allow the passage of larger molecules (4-6 nm). In order to reach the bloodstream in the endothelial vasculature, proteins and peptides must cross this alveolar epithelium, the capillary endothelium, and the intervening extracellular matrix. 

King M. Mucus, mucociliary clearance and coughing. In Bates DV, ed. Respiratory Function in Disease. 3rd ed. Philadelphia WB Saunders, 1989 69-78. 

Disruption of these defense mechanisms can lead to bacterial colonization or viral infection. Mucus temperature is important in controlling respiratory infections because decreasing below central body core temperature not only impairs ciliary movement,hut also enhances viral replication,- greatly increasing the likelihood of respiratory infection. Drying of airway mucus also increases the possibility of respiratory infection by reducing mucus thickness and impairing mucociliary clearance, i- i--... 

The particle size is the most important factor that contributes to the clearance of particles. For particles deposited in the anterior parts of the nose, wiping and blowing are important mechanisms whereas particles on the other areas of the nose are removed with mucus. The cilia move the mucus toward the glottis where the mucus and the particles are swallowed. In the tracheobronchial area, the mucus covering the tracheobronchial tree is moved upward by the cilia beating under the mucus. This mucociliary escalator transports deposited particles and particle-filled macrophages to the pharynx, where they are also swallowed. Mucociliary clearance is rapid in healthy adults and is complete within one to two days for particles in the lower airways. Infection and inflammation due to irritation or allergic reaction can markedly impair this form of clearance. 

Mussatto, D.J., Garrad, C.S. and Lourenco, R.V (1988). The effect of inhaled histamine on human tracheal mucus velocity and bronchial mucociliary clearance. Am. Rev. Respir. Dis. 138 775-779. 

Mucociliary Clearance Mucociliary clearance operates by the coordinated movements of cilia, which sweep mucus out of the lungs towards the pharynx where it is swallowed. There is an inverse relationship between mucus velocity and airway generation, which relates to the lower percentage of ciliated cells, shorter cilia, lower ciliary beat frequency and lower number of secretory cells in the peripheral airways [121]. The reported tracheal mucociliary clearance... 

Mucociliary clearance Inhaled particles are cleared from the airways through trapping of the particles in mucus upon deposition and subsequent clearance of the mucus (with trapped particles) which is propelled by the coordinated beating of cilia towards the throat. This is termed the mucociliary escalator system. The mucociliary function is regulated by a variety of factors, such as bradykinin, histamine and cytokines [20-24],... 

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. 

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. ... 

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. 

Bioadhesive formulations and microsphere delivery systems in particular have attracted much attention. As drug formulations are usually rapidly removed from the site of deposition by the mucociliary clearance, increasing the retention time of drug in the nasal cavity via bioadhesion can increase bioavailability [28], Bioadhesion may be defined as the ability of a material (synthetic or biological) to adhere to a biological tissue for an extended period of time. When applied to a mucous membrane, a bioadhesive polymer may adhere primarily to the mucus layer or epithelial cell surface in a phenomenon known as mucoadhesion [29,30]. The bioadhesive properties of a wide range of materials have been evaluated over the last decade. 

Chronic diseases include cystic fibrosis in which nasal mucus is thick and viscous as a result of abnormal chloride transport across the membrane of the epithelial cells, leading to reduced water secretion. Similarly, chronic sinusitis also reduces nasal mucociliary clearance due to an increase in the rheological properties of mucus. 

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. 

The mucus layer also bathes the cilia of ciliated epithelial surface cells and provides a stimulus for ciliary motility (i.e., ciliary beating). The cilia consist of microtubules with a 9 + 2 configuration (nine pairs of peripheral microtubules and two central microtubules) that beat rhythmically to rapidly move mucus from the anterior to the posterior portion of the nasal cavity. To successfully cross the nasal permeability barrier, peptide drugs must penetrate the mucus layer and cross the epithelial cell layer, and do so in a limited time, because mucociliary clearance will limit the time of exposure of the peptide to the absorptive surface [19-21,27-29], Typically, drugs or inspired particles that are delivered nasally are removed via mucociliary clearance, with a clearance time of approximately 15 min in humans however, this transit time can vary from person to person and can be impacted by the addition of mucoadhesive agents to the formulation [30-37],... 

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... 

In addition to its involvement in mucociliary clearance, mucus can also affect drug delivery by interacting directly with nasally administered drugs by ... 

Particles and dissolved drags entrapped in the mucus will be removed from the TB region via mucociliary clearance within a few hours after being deposited. This provides an efficient self-cleansing mechanism. 

Mucociliary clearance is an organized, complex process which is highly dependent upon the composition and depth of the epithelial lining fluid and the viscoelastic properties of the mucus. In many airways diseases there is hypersecretion of mucus. This may cause an overloading of the ciliary transport process, resulting in... 

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