Oral mucosa epithelium

Advantages of the oral mucosal route of delivery include its capacity to bypass all the limitations associated with the oral route, ease of administration, relatively low content of enzymes, and adequate vascular drainage. As described in the following sections, most of the limitations of the oral mucosa epithelium arise from its stratified nature and its intercellular content characteristics. Nonetheless, due to its direct connection to systemic circulation, delivery systems could potentially be formulated to show either bolus-like or controlled release profiles for specific therapeutic needs. Polymers used in the development of such delivery systems play a major role in the release profile, permeation enhancement, and the localization of the active in the vicinity of the absorbing mucosa. Among the various uses of polymers in delivery systems, their mucoadhesive nature is the most prominent application in the oral mucosal route and is the main focus of this entry. After describing the physiological considerations in the oral cavity mucosa, this entry will review the literature pertinent to the use of polymers in delivery systems for the oral mucosal route. 

Signs and Symptoms Easily confused with foot-and-mouth disease (C18-A017). Symptoms include fever, ulcers and erosions of the oral mucosa, sloughing of the epithelium of the tongue, and lesions at the mucocutaneous junctions of the lips, chewing movements and drooling (ptyalism), crusting lesions of the muzzle. Blisters, ulcers, and erosion of the coronary bands, and teats. 

There has also been a report regarding the active transport of antibacterial agents in oral mucosa. In a cell line derived from oral epithelium, the uptake of ciprofloxacin and minocycline was not only saturable and inhibited in the presence of other compounds, but the intracellular levels of both antibiotics were 8 10-fold higher than the extracellular levels as well, demonstrating an active transport process [18]. Whether the permeability of these compounds across the entire oral mucosa occurs via an active transport process, however, remains to be determined. 

Chen SY, Squier CA (1984) The ultrastructure of the oral epithelium. In Meyer J, Squier CA, Gerson SJ (eds.) The Structure and Function of Oral Mucosa. Pergamon Press, Oxford, pp 7-30... 

The oral mucosa is anatomically divided into three tissue layers (Fig. 1) [10] the epithelium, the basement membrane, and the connective tissues. 

The cheeks, lips, hard and soft palates and tongue form the oral cavity. The main difference between the oral mucosa and skin as compared to the gastrointestinal (GI) tract lining lies in the organization of the different epithelia. While the latter has a single layer of cells forming the simple epithelium, the skin and the oral cavity have several layers of cells with various degrees of differentiation. 

The factors that hinder the absorption of peptides through the intestinal epithelium, namely high molecular weight, charge, and hydrophilicity also affect their absorption through the oral mucosa. Combinations of mucoadhesive systems, absorption enhancers, and enzyme inhibitors have enabled better absorption. 

Qualitative in-life biomarkers that are characteristic of chronic exposure to white phosphorus include progressive destruction of the jaw bones (phossy jaw), brittleness of long bones, and poor healing of oral cavity lesions including tooth sockets after tooth extraction (see Section 2.2 for details). In-life biomarkers that are probably shared with other toxic compounds include increased permeability of capillary walls and impaired microcirculation. Postmortem qualitative biomarkers include hyperkeratosis of the epithelium of the oral mucosa and lesions of the capillary walls (see Section 2.2 for details). Hyperkeratosis is a microscopic morphological finding that can be seen in biopsy material from a living patient or from an autopsy and is seen in association with phosphorus intoxication. 

The oral mucosa provides a protective covering for underlying tissues while acting as a barrier to the entry of microorganisms and toxins. Histologically, the stratified squamous epithelium lining the oral cavity exhibits a diverse structure as well as important inter-species differences. This... 

The process of maturation from basal cell through to desquamation (shedding) has been estimated at 13 days for the buccal epithelium and this process is probably representative of the oral mucosa as a whole. Thus the rate of cell turnover in the oral cavity is considerably faster than that of skin, which takes approximately 30 days (see Section 8.2.1). 

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. 

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. 

The major function of the oral epithelium is to provide a protective surface layer between the oral environment and the deeper tissues. The oral epithelium has a squamous epithelium of tightly packed cells that form distinct layers by a process of maturation from the deeper layers to the surface. The pattern of maturation differs in different regions of the oral mucosa... 

Oral mucosae are composed of multiple layers of cells, which show various patterns of differentiation dependent on the functions of different regions in the oral cavity. The oral mucosa is covered by a stratified, squamous epithelium, and three different types of mucosa can be distinguished the masticatory, the lining, and the specialized mucosa. Blood supply to the oral cavity tissues is delivered via the external carotid artery, which branches to the maxiliary lingual and facial artery. There are no mucus-secreting goblet cells in the oral mucosa, but mucins are found in human saliva. These mucins are water-soluble and form a gel of 10-200 pm thickness. Saliva, mainly composed of water (99%), is continuously secreted in the oral cavity and exists as a film with a thickness of 0.07-0.1 mm. ... 

Cigarette smoke is more acidic than pipe or cigar smoke and requires inhalation into the lungs for effective uptake of nicotine. In contrast, nicotine administered via pipes or cigars is more readily absorbed through the oral mucosa (Musk and de Klerk 2003). In the lungs, the large surface area of the respiratory epithelium is exposed to the smoke, which promotes the absorption of nicotine. This provides a more immediate sense of satisfaction for the smoker and potentiates a rapid addiction to nicotine. 

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