Buccal proteins

The use of a bioadhesive, polymeric dosage form for sustained dehvery raises questions about swallowing or aspirating the device. The surface area is small, and patient comfort should be addressed by designing a small (less than 2 cm ), thin (less than 0.1 mm (4 mil) thick) device that conforms to the mucosal surface. The buccal route may prove useful for peptide or protein dehvery because of the absence of protease activity in the sahva. However, the epithelium is relatively tight, based on its electrophysiological properties. An average conductance in the dog is 1 mS/cm (57) as compared to conductances of about 27 and 10 mS/cm in the small intestine and nasal mucosa, respectively (58,59) these may be classified as leaky epitheha. 

Bacterial catabolism of oral food residue is probably responsible for a higher [NHj] in the oral cavity than in the rest of the respiratory tract.Ammonia, the by-product of oral bacterial protein catabolism and subsequent ureolysis, desorbs from the fluid lining the oral cavity to the airstream.. Saliva, gingival crevicular fluids, and dental plaque supply urea to oral bacteria and may themselves be sites of bacterial NH3 production, based on the presence of urease in each of these materials.Consequently, oral cavity fNTi3)4 is controlled by factors that influence bacterial protein catabolism and ureolysis. Such factors may include the pH of the surface lining fluid, bacterial nutrient sources (food residue on teeth or on buccal surfaces), saliva production, saliva pH, and the effects of oral surface temperature on bacterial metabolism and wall blood flow. The role of teeth, as structures that facilitate bacterial colonization and food entrapment, in augmenting [NH3J4 is unknown. 

Possible noninvasive routes for delivery of proteins include nasal, buccal, rectal, vaginal, transdermal, ocular, oral, and pulmonary. For each route of delivery there are two potential barriers to absorption permeability and enzymatic barriers. All of the... 

Penetration enhancers are low molecular weight compounds that can increase the absorption of poorly absorbed hydrophilic drugs such as peptides and proteins from the nasal, buccal, oral, rectal, and vaginal routes of administration [186], Chelators, bile salts, surfactants, and fatty acids are some examples of penetration enhancers that have been widely tested [186], The precise mechanisms by which these enhancers increase drug penetration are largely unknown. Bile salts, for instance, have been shown to increase the transport of lipophilic cholesterol [187] as well as the pore size of the epithelium [188], indicating enhancement in both transcellular and paracellular transport. Bile salts are known to break down mucus [189], form micelles [190], extract membrane proteins [191], and chelate ions [192], While breakdown of mucus, formation of micelles, and lipid extraction may have contributed predominantly to the bile salt-induced enhancement of transcellular transport, chelation of ions possibly accounts for their effect on the paracellular pathway. In addition to their lack of specificity in enhancing mem-... 

Genetic tests are performed on a sample of blood, hair, skin, amniotic fluid (the fluid that surrounds a fetus during pregnancy), or other tissue. For example, a procedure called a buccal smear uses a small brush or cotton swab to collect a sample of cells from the inside surface of the cheek. The sample is sent to a laboratory where technicians look for specific changes in chromosomes, DNA, or proteins, depending on the suspected disorder. The laboratory reports the test results in writing to a person s doctor or genetic counselor. 

The buccal mucosa, which lines the inside of the cheek, has been investigated as an alternative route for drug delivery, especially for proteins and peptides. There are many advantages associated with the use of the buccal mucosa as a site for the delivery of drugs into the systemic circulation. Since blood flow from the buccal epithelium drains directly into the internal jugular... 

Senel S, Kremer M, Nagy K, Squier C (2001) Delivery of bioactive peptides and proteins across oral (buccal) mucosa. Curr Pharm Biotechnol 2 175-186... 

As noted earlier, the choice of species for experimentation is critical due to anatomical differences and it may also reflect species, as well as individual, differences in the expression/activity of transporter and metabolic proteins [43, 44], Since the fraction absorbed across buccal mucosa in vivo is not established for many compounds in different species including humans, the potential existence of a correlation between in vitro permeability coefficients in freshly isolated pig, dog, monkey, and human buccal mucosa was investigated (Figure 7.3). The correlation coefficient obtained for porcine and canine tissue was poor (0.65 and 0.67, respectively, at the 95% confidence level). Results for relatively high permeability compounds in porcine tissue resemble those previously reported where permeability coefficients were by an order of magnitude... 

Portero A, Remunan-Lopez C, and Nielsen HM (2002) The potential of chitosan in enhancing peptide and protein absorption across the TR146 cell culture model—An in vitro model of the buccal mucosa. Pharm. Res. 19 169-174. 

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