Nasal epithelium transport

Radon daughters are deposited on the surface of mucus lining the bronchi. It is generally assumed that the daughter nuclides, i.e. polonium-218 (RaA), lead-214 (RaB) and bismuth-214 (RaC), remain in the mucus and are transported towards the head. However, one dosimetric model assumes that unattached radon daughters are rapidly absorbed into the blood (Jacobi and Eisfeld, 1980). This has the effect of reducing dose by about a factor of two. Experiments in which lead-212 was instilled as free ions onto nasal epithelium in rats have shown that only a minor fraction is absorbed rapidly into the blood (Greenhalgh et al., 1982). Most of the lead remained in the mucus but about 30% was not cleared in mucus and probably transferred to the epithelium. 

Cremaschi et al. [39] investigated transepithelial pathways of eel calcitonin, corticotrophin, sucrose, and polyethylene glycol-4000 (PEG-4000) transport across the nasal epithelium using rabbit nasal mucosa mounted on Ussing chamber that was maintained at 27°C. The electrical parameters of the tissues were those of leaky epithelium that allow macromolecules to permeate paracellularly their observation was similar to the finding made by McMartin et al. [40] in which the authors described the nasal epithelium as leaky with... 

Schmidt MC, Simmen D, Hilbe M, Boderke P, Ditzinger G, Sandow J, Lang S, Rubas W, Merkle HP (2000) Validation of excised bovine nasal mucosa as in vitro model to study drug transport and metabolic pathways in nasal epithelium. J Pharm Sci 89 396-407. 

This refers to the transport across the epithelial cells, which can occur by passive diffusion, carrier-mediated transport, and/or endocytic processes (e.g., transcytosis). Traditionally, the transcellular route of nasal mucosa has been simply viewed as primarily crossing the lipoidal barrier, in which the absorption of a drug is determined by the magnitude of its partition coefficient and molecular size. However, several investigators have reported the lack of linear correlation between penetrant lipophilicity and permeability [9], which implies that cell membranes of nasal epithelium cannot be regarded as a simple lipoidal barrier. Recently, compounds whose transport could not be fully explained by passive simple diffusion have been investigated to test if they could be utilized as specific substrates for various transporters which have been identified in the... 

Since the uptake of particles in nasal epithelial tissue is known to be mostly mediated by M cells, nasal administration has been investigated as a noninva-sive delivery of vaccines [37], However, since the uptake of naked DNA by endocytocis is limited, use of either nanoparticles as mucosal delivery systems [37] or hypotonic shock [38] is reported for the efficient transfection of gene and vaccine into the nasal epithelium. It was also reported that polypeptides and polypeptide-coated nanospheres (diameter about 500 nm) are transported through endocytic process in rat M cells [39],... 

R. Agu, H. V. Dang, M. Jorissen, T. Willems, S. Vandoninck, J. Van Lint, J. V. Vandenheede, R. Kinqet, and N. Verbeke. In vitro polarized transport of L-phenylalanine in human nasal epithelium and partial characterization of the amino acid transporters involved. Pharm Res 20 1125-1132 (2003). 

U. Werner and T. Kissel. In-vitro cell culture models of the nasal epithelium A comparative histochemical investigation of their suitability for drug transport studies. Pharm Res 13 978-988 (1996). 

T. Kissel and U. Werner. Nasal delivery of peptides An in vitro cell culture model for the investigation of transport and metabolism in human nasal epithelium. J Control Release 53 195-203 (1998). 

Drug absorption occurs from the site(s) of drug absorption (e.g., gut, lung, nasal epithelium) by either active (e.g., transport mediated) or passive mechanisms. The bioavailability (F) of a drug is the fraction that reaches the systemic circulation and is ultimately avail-... 

Shipley MT Transport of molecules from nose to brain transneuronal anterograde and retrograde labeling in the rat olfactory system by wheat germ agglutinin-horseradish peroxidase applied to the nasal epithelium. Brain Res Bull 15 129-142, 1985... 

The nasal epithelium possesses selective absorption characteristics similar to those of a semipermeable membrane, i.e., it allows a rapid passage of some compounds while preventing the passage of others. The process of transportation across the nasal mucosa involves either passive diffusion, via paracellular or transcellular mechanisms, or occurs via active processes mediated by membrane-bound carriers or membrane-derived vesicles involving endo- or transcytosis. 

Lipophilic drug molecules are absorbed across the nasal epithelium by passive transcellular diffusion. For small, unionized molecules, this provides a rapid efficient transport mechanism, often resulting in plasma concentration profiles resembling that of intravenous injection and bioavailabilities of up to 100%. 

Mucociliary clearance can be studied in vivo in humans using gamma scintigraphy to follow the clearance of radiolabeled solutions from the nasal cavity or by measuring the transport rate of radiolabeled markers administered to the nasal epithelium. Simpler methods are used to monitor the appearance of a strongly colored dye (by visual inspection) or sweet tasting substance such as saccharin (by taste) at the pharyngeal cavity. 

Active transport mechanisms for di- and tri-peptides, as well as L-amino acids, have been demonstrated in the nasal epithelium. 

Plus laboratory evidence of a CFTR abnormality as documented by elevated sweat chloride concentrations or identification of two CF mutations or m vivo demonstration of characteristic abnormalities in ion transport across the nasal epithelium... 

Figure 6. Amino acid-induced activity patterns were examined in more detail using the calcium-sensitive dye CalciumGreen (Friedrich and Korsching 1997). Like ANEPPQ, this dye was introduced by anterograde transport from the nasal epithelium and thus labeled only the axons and terminals of the olfactory receptor cell axons. In contrast to the voltage-sensitive dye, signals originate only in terminal presynap-tic regions, and are therefore more focal in nature than those of the voltage-dependent dye, which originate from both axons and terminals.

Demski and Northcutt (1983) did find, however, that application of horseradish peroxidase to the nasal epithelium resulted in transport of this enz3mie to the TN ganglion and its axon terminals in the telencephalon, suggesting proximity of TN dendrites and olfactory epithelium. Indeed, immunocytochemical visualization of the TN of goldfish revealed processes extending from the ganglion cells along the branches of the olfactory nerves to the base of the olfactory lamellae, but no processes were observed in the sensory epithelium itself (Kyle, unpublished results). Clearly, a role for the TN in pheromone detection has yet to be established. 

The thin, porous and highly vascularised nasal epithelium has a high total blood flow, which facilitates fast absorption of substances. Direct transport to the systemic circulation or the central nervous system makes it possible to obtain a rapid therapeutic effect. The intranasal absorption depends on the mucociliary clearance, pathological conditions such as infections, allergy and obstruction, mucus secretion, moisture content, enzymatic degradation, and blood flow. It should be remembered that the blood flow can be affected by either locally or systemically active substances. These phenomena can determine the nasal absorption of substances. Oxymetazoline and clonidine reduce the blood flow, while phenylephrine and salbutamol raise it. 

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