Frontal sinus Frontal bone

Olfactory Superior Middle turbinate Inferior turbinate Vestibule Maxilla

Figure 2.8 Structure of the nasal cavity.

Apart from the columnar cells (ciliated and nonciliated), the nasal epithelium also consists of basal and goblet cells.45 The ciliated and non-ciliated columnar cells are connected by tight junctions and are covered with microvilli (~300 microvilli per cell).111 The 4- to 6-|jm-long cilia beat the overlying mucus layer at a frequency of 1000 strokes per minute and propel the mucus from the anterior to the posterior part of the nasal cavity.107 The cilia in the nasal vestibule and the mucus layer covering the respiratory area of the nasal cavity trap particulates, which are then carried down to the esophagus by the mucociliary clearance mechanism.107

Nasal mucus. The nasal mucus protects the body against airborne substances. Nasal mucus consists of mucopolysaccharides complexed with sialic acid, sloughed epithelial cells, bacteria, water (95 percent), glycoproteins and lipids (0.5 to 5 percent), mineral salts (0.5 to 1 percent), and free proteins (albumin, immunoglobulins, lysozyme, interferon, lactoferin, etc., 1 percent).13,45,111,112 The surface pH of the nasal mucosa is 5.5 to 6.5.113

Barriers affecting nasal absorption. Unlike other biological membranes, it was noted that physicochemical properties such as charge and lipophilicity might not be of significant importance for transnasal drug delivery of drugs with a molecular weight of less than 300 Da. It has been hypothesized that the absorption of small molecules takes place via the aqueous channels of the membrane.106'114

Anatomical and physiological factors that influence nasal absorption include membrane transport' deposition' enzyme degradation' and mucociliary clearance.106'115 The relative bioavailability of small lipophilic drugs delivered by this route approaches 100 percent owing to good absorption.107 However, the bioavailability of macromolecules such as proteins and polar drugs larger than 1000 Da is low and ranges from 0.5 percent to 5 percent owing to low permeability through the membrane.107'108

The nasal route of drug delivery avoids the liver first-pass effect, but the pseudo-first-pass effect owing to nasal metabolism of drugs is still a concern. Many enzymes such as carboxylesterase, aldehyde dehydrogenase, glutathione transferases, UDP-glucoronyl transferase, epoxide hydrolases, CYP-dependent monoxygenases, exo- and endopeptidases and proteases are present in the nasal mucosa.106108,110,116 CYP enzymes are present abundantly in the olfactory epithelium.107,110

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 mechanism transports the particles down the throat.107,108 Mucociliary clearance can be affected by the drug moiety, formulation, hormones, and disease states.108

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