Mucociliary mechanism

Pavia, D., Short, M.D. Thomson, M.L. (1970) No demonstrable long term effects of cigarette smoking on the mucociliary mechanism of the human lung. Nature, 226, 1228-31. 

Lead particles with an aerodynamic diameter > 5 pm are mainly deposited in the upper airways, cleared by the mucociliary mechanism, and then swallowed (Skerfving... 

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--... 

Proctor, D. E, Andersen, E, and Lundqvist, G. R. (1977b), Nasal mucociliary funerion in humans, Part 1. In Respiratory Defense Mechanisms pp. 427- 52. Marcel Dekkcr, New York. 

Mucociliary escalator Mechanism that removes extracellularly-derived materials from the conducting airways by entrapping these materials in mucus that is continuously moved toward the epiglottis by synchronized ciliary movement. 

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. 

Several groups investigated the use of liposomes for the intra-pulmonary delivery. Farr et al. (1985) showed that the deposition of aerosolized liposomes in the human lung depends on the aerosol particle size. Short-term retention profiles for MLVs and SUVs deposited in the lung were indicative of clearance via the mucociliary transport mechanism. 

The first purified and characterized drug substances were administered as aerosols as a topical treatment for asthma approximately 50 years ago. More recently, drugs have been evaluated for systemic delivery. For each category of drug the mechanism of clearance from the airways must be considered. These mechanisms may be listed as mucociliary transport, absorption, and cell-mediated translocation. The composition and residence time of the particle will influence the mechanism of clearance. 

A sophisticated respiratory host defence system has evolved to clear airborne particles and potential pathogens in inspired air [106, 143], The system comprises mechanical (i.e. air filtration, cough, sneezing and mucociliary clearance), chemical (antioxidants, antiproteases and surfactant lipids) and immunological defence mechanisms and is tightly regulated to minimise inflammatory reactions [92, 143],... 

From a drug delivery perspective, the components of the host defence system comprise barriers that must be overcome to ensure efficient drug deposition as well as retention in and absorption from the respiratory tract. Important non-absorptive clearance mechanisms include mucociliary clearance, alveolar macrophages and metabolism (Figure 6.2). 

Aerosols must be respirable, that is, have a mean aerodynamic diameter of less than 5 xm, to ensure that a reasonable proportion will penetrate the respiratory tract defence systems of the nasal passages and the mucociliary clearance mechanisms. 

Substances deposited in the nasal cavity that are not readily absorbed are cleared in about 15 to 20 minutes by mucociliary clearance. The mucociliary clearance mechanism affects the absorption of polar drugs that have low permeability across membranes. This defense mecha-nism transports the particles down the throat. Mucociliary clearance can be affected by the drug moiety, formulation, hormones, and disease states.108... 

The tracheobronchial or conducting airways, which provide the channels for gas transport but have no gas-exchange function. Their surface is ciliated to provide a particle clearance mechanism called mucociliary clearance. 

There are two important defense mechanisms against inhaled particles. The first of these involves the mucociliary escalator and consists of the trapping of particles in mucus followed by the upward movement of the mucus brought about by the upward beating of cilia on the airway epithelial airway cells. The material is then either swallowed or expectorated. The second mechanism is macrophage mediated. Macrophages engulf particles and either deposit them on the mucociliary escalator or enter the lymphatic system. 

---