Sublingual epithelium

Of the different types of oral mucosal cell cultures that have been used [47,48], the most commonly used ones are explants of primary cultures. Small pieces of excised buccal or sublingual tissue are placed in a support system and fed with culture medium. The outgrowths obtained from these tissue explants are then transferred and grown in appropriate media. For example, outgrowths of fibroblasts [49] thus obtained have been described. Gibbs and Ponec [50] reconstructed the epithelium of mucosal tissue by placing a tissue biopsy (with the epithelial side upwards) onto a fibroblast-populated collagen gel. The explants obtained were cultured immediately at the air liquid interface until the epithelium had expanded over the gel (2-3 weeks). These explant cultures may retain many of the in vivo tissue characteristics. 

Drags administered orally must cross the GI tract epithelium to be absorbed and enter the systemic circulation. Similarly, drags administered by alternative routes, such as the buccal, sublingual, nasal, pulmonary and vaginal routes, must all cross the appropriate epithelial interfaces to reach the general circulation. The types of epithelial interfaces, the barriers they pose to drag absorption, and the routes and mechanisms of drag absorption across these interfaces, are described below. 

Keratinized epithelium is dehydrated, mechanically tough and chemically resistant. It is found in areas of the oral cavity subject to mechanical stress such as the mucosa of the gingiva (gums) and hard palate (roof of mouth). Non-keratinized epithelium is relatively flexible and is found in areas such as the soft palate, the floor of the mouth, the lips and the cheeks. Thus the regions of the oral cavity pertinent to drag delivery (i.e. the sublingual and buccal regions) have a non-keratinized epithelium. 

Figure 7.1 Structure of non-keratinized oral epithelium, as found in the sublingual and buccal regions of the oral cavity. (Note keratinized epithelium has a broadly similar structure however, the epithelial cell layers comprise basal layer, prickle cell layer, granular layer and keratinized layer)...

The permeability of the oral mucosal epithelium is intermediate between that of the skin epithelium, which is highly specialized for a barrier function (see Section 8.1) and the gut, which is highly specialized for an absorptive function. Within the oral cavity, the buccal mucosa is less permeable than the sublingual mucosa. 

The sublingual mucosa is much thinner, approximately 100- 200 /mi. The thin epithelium of the sublingual mucosa means that extremely rapid absorption is possible via this route. 

A rich blood supply and lymphatic network in the lamina propria serve the oral cavity, thus drag moieties which traverse the oral epithelium are readily absorbed into the systemic circulation. The blood flow in the buccal mucosa is 2.4 mL min 1 cm 2 whereas that to the sublingual mucosa is 0.97 mL min-1 cm 2. 

With sublingual or buccal application, the drug encounters the nonkeratinized, multilayered squamous epithelium of the oral mucosa. Here, the cells establish punctate contacts with each other in the form of des-mosomes (not shown) however, these do not seal the intercellular clefts. Instead, the cells have the property of sequestering polar lipids that assemble into layers within the extracellular space (semicircular inset, center right). In this manner, a continuous phospholipid barrier arises also inside squamous epithelia, although at an extracellular location, unlike that of intestinal epithelia. A similar barrier principle operates in the multilayered keratinized squamous epithelium of the skin. 

Sublingual medications are administered under the tongue. Buccal medications are administered between the cheek and the gum. Both routes absorb medication quickly into the circulatory system because there is a vast network of capillaries beneath the thin layer of epithelium tissue in those areas. 

These medications are quickly absorbed into the circulatory system because the tissues beneath the tongue and between the cheek and gum consist of a thin layer of epithelium cells and a vast network of capillaries. Nitroglycerin can be administered sublingually. 

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