Nasal administration mucociliary clearance

The extent of drug absorption following nasal administration depends to a reasonable extent on the ease with which a drug molecule crosses the nasal epithelium without degradation or rapid clearance by the mucociliary clearance system. The effects of these two elimination components are more pronounced for proteins and peptides. The nasal administration of drugs, especially proteins and peptides, as well as other molecules has been studied with excised tissues harvested from rabbit, cow, sheep, and pig species (Table 5.2). A... 

Direct toxic effects such as irritation, inflammation, or increased permeability will bring about symptoms such as the sneeze reflex, nasal discomfort, and hypersecretion with the possibility of underlying pathological changes such as squamous metaplasia, cilia erosion, plasma exudation, epithelial necrosis, inflammatory remodeling, or neutrophil accumulation. Indirect adverse effects can also occur and any alteration to normal nasal homeostasis should be avoided. For example, a reduction in mucociliary clearance can cause rhinitis, sinusitis, and an increased susceptibility to airway infections, and consequently ciliary movement should not be altered by any nasal medication. In the context of absorption enhancers, the rate and extent of recovery of normal nasal epithelial function after nasal administration is a prime consideration. 

The use of degradable starch microspheres has proved to be well tolerated in both experimental animals and humans. No alterations of nasal mucosa were detected after eight weeks of nasal administration of starch microspheres to rabbits. Additionally, a preliminary test on healthy volunteers also showed good acceptability [62], Another study of healthy volunteers revealed no changes in mucociliary clearance or in the geometry of the nasal cavities after eight days of nasal administration of dry starch microspheres [87],... 

In conclusion, in order to make predictions regarding the safety of the nasal formulation on mucociliary clearance, both in vitro and in vivo studies have to be performed. It is also essential to determine long-term use effects in animals and in humans if the nasal formulation is intended for subchronic or chronic administration. 

Fig. 2 Possible transportation routes of drugs after nasal administration. MCC = mucociliary clearance BBB = blood-brain barrier BCSFB = blood SF barrier.

Upon intranasal administration, a drug is not as susceptible to dilution and first-pass effects as in oral delivery.46 47 The nasal route may also be an effective means of delivering drugs to the brain 46 Barriers to nasal delivery include the enzymes of the nasal mucosa, the epithelial barrier, the mucus layer, and limited absorption time resulting from mucociliary clearance.48... 

In general, retention of the product within the nasal cavity will be attained if the vast majority of the particles or droplets are larger than 10 pm. The deposition site of the formulation is important and therefore also the container and dosing device and the way of administration. When using a spray the solution is finely distributed in the anterior part of the nose and mucociliary clearance causes the formulation to... 

As a consequence of the mucociliary clearance of the nasal cavity active substances that are tmable to pass the nasal membrane will end up in the oropharynx and are swallowed into the gastro-intestinal tract, from where they may be absorbed. This gastro-intestinal absorption after nasal administration may erroneously be considered as nasal absorption. Such a phenomenon may, for example, occur when the nasal spray of the anti-migraine medicine sumatriptan is used. 

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