chitosan and plga microspheres as drug delivery ... - UniCA Eprints

1. General Introduction1.4.5. Respiratory PatternsThe pattern of respiration during aerosol exposure influences regional deposition, sincebreathing volume and frequency determine the mean flow rates in each region of therespiratory tract, which, in turn, influence the effectiveness of each deposition mechanism(91, 97, 98, 99). Turbulence tends to enhance particle deposition, the degree of potentiationdepending on the particle size. Rapid breathing is often associated with increased depositionof larger particles in the upper respiratory tract, while slow, steady inhalation increases thenumber of particles that penetrate to the peripheral parts of the lungs (100). Slow breathing,with or without breath-holding, showed a broad maximum deposition in the ciliated airways(tracheobronchial region). The pulmonary maximum occurred between 1.5 µm and 2.5 µmwith breath-holding and between 2.5 µm and 4µm without breath-holding. Rapid inhalationshowed similar trends: the tracheo-bronchial region maximum falls and shifts to between 3µm and 6 µm. Pulmonary deposition sharpens and occurs between 1.5 µm and 2 µm withbreath-holding, and between 2 µm and 3 µm without breathholding. When the aboveconsiderations are taken into account, the ideal scenario for aerosol would be: (1) aerosol ADsmaller than 5 µm, to minimize oropharyngeal deposition, (2) slow, steady inhalation, and (3)a period of breath-holding on completion of inhalation.1.4.6. Pulmonary ClearanceThe primary function of the pulmonary defensive response to inhaled particles is to keep therespiratory surfaces of the alveoli clean and available for respiration. The elimination ofparticles deposited in the lower respiratory tract serves an important defence mechanism toprevent potentially adverse interactions of aerosols with lung cells. Insoluble particulates arecleared by several pathways, which are only partially understood. These pathways are knownto be impaired in certain diseases and are thought to depend on the nature of the administeredmaterial (101, 102). Swallowing, expectoration, and coughing constitute the first sequence ofclearance mechanisms operating in the naso/oropharynx and tracheobronchial tree.A major clearance mechanism for inhaled particulate matter deposited in the conductingairways is the mucociliary escalator, whereas uptake by alveolar macrophages (86, 103)predominates in the alveolar region. In addition to these pathways, soluble particles can alsobe cleared by dissolution with subsequent absorption from the lower airways. The rate ofparticle clearance from these regions differs significantly and its prolongation can haveserious consequences, causing lung diseases from the toxic effects of inhaled compounds. It isnow well recognized that the lungs are a site for the uptake, accumulation, and/or metabolism23