Human nasal cell lines

To overcome the serious issue of the short supply and lack of reproducibility of human nasal tissues, enthusiastic studies have been performed to establish cell lines with extended in vitro lifespans. Currently, no human nasal cell lines have yet been established for overall biopharmaceutical purposes (i.e., both permeation study and metabolic study). Only a human nasal cell line RPMI 2650, originating from an anaplastic nasal septum, has been gaining attention for use in metabolic studies as a significant enzymatic barrier, similar to the excised human nasal tissue. ° ... 

In vitro methods to measure ciliary beat frequency can be performed on explants of ciliated mucosa [64] or on different types of ciliated cells, such as ciliated chicken embryo trachea cells [123], nasal cell lines derived from carcinomas of epithelial origin (RPMI2650, BT, NAS 2BL), or human lung adenocarcinoma cell line Calu-3... 

RPMI 2650 is the only human nasal epithelial cell line derived from a spontaneously formed tumor. This particular cell line has been mostly used for nasal metabolism studies, since it grows into a multilayer and does not form confluent monolayers (although perijunctional actin rings are present). Thus, RPMI 2650 cell monolayer is rarely used for nasal transport studies [44, 58],... 

Various in vitro systems are currently available, which include the excised nasal epithelium from different animal species, primary cell cultures, and cell lines, of the human nasal epithelium. The technical details are given in the recent distinguished review.f ... 

De Fraissinette, A. Brun, R. Felix, H. Vonderscher, J. Rummelt, A. Evaluation of the human cell line RPMI 2650 as an in vitro nasal model. Rhinology 1995, 35 (4), 194-198. 

Lysozyme (LZ) is an enzyme that is abundantly present in the mucosal membranes that line the human nasal cavity and tear ducts. It can also be found in high concentration in egg white. LZ destroys bacterial cell walls by hydrolyzing the polysaccharide component of the cell wall. Human milk contains 0.4 g/liter of LZ, an enzyme that contributes to antibacterial activity in human milk. 

Since its discovery, isolation, and purification in the early twentieth century, insulin has been administered to diabetic patients exclusively by injection until the recent introduction of inhaled insulin. Insulin possesses certain physiochemical properties that contribute to its limited absorption from the gastrointestinal tract, and requires subcutaneous injection to achieve clinically relevant bioavailability. With a molecular size of 5.7 kDa, insulin is a moderately sized polypeptide composed of two distinct peptide chains designated the A chain (21 amino acid residues) and the B chain (30 amino acid residues) and joined by two disulfide bonds. Like all polypeptides, insulin is a charged molecule that cannot easily penetrate the phospholipid membrane of the epithelial cells that line the nasal cavity. Furthermore, insulin monomers self-associate into hexameric units with a molecular mass greater than 30 kDa, which can further limit its passive absorption. Despite these constraints, successful delivery of insulin via the nasal route has been reported in humans and animals when an absorption enhancer was added to the formulation. 

The mechanism of olfaction has many theories but is not fully understood and is still the subject of research. The nose is the human organ that detects smell (Fig. 5.9). It extends from the face to the end of the palate. In its simplest explanation the two nasal cavities are lined with a mucous membrane, kept moist by the secreted substance mucus. Chemicals in the air entering the nose must dissolve in this mucus before they can be detected. A small area - about the size of a small postage stamp - in the upper part of the nasal cavity contains olfactory cells, which are sensitive to the chemicals in the mucus solution. For a molecule to be detected it must bind specifically to the sensitive cells that act as sensory receptors. The sensory receptors situated in the olfactory epithelium (epithelium is the name given to the outer layer of covering cells) are believed to bind specifically with substances according to the shape of their molecules. 

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