Oral mucosa permeability

The function of the mucosal pellicle is to serve as a barrier between the oral epithelial surface and the external environment, and so it may also act as a barrier to drug delivery. However, there are limited studies assessing the role of the mucus layer in buccal permeability. In one study, treatment of the oral mucosa with anticholinergic agents resulted in an increased permeability of certain compounds, and it was suggested that the reduced salivary flow may have been responsible for the reduced barrier properties of the tissue [113]. In... 

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. 

One of the most common in vivo methods used to assess the permeability of the buccal mucosa is the buccal absorption test of Beckett and Triggs [13]. In this test, a known volume of a drug solution is introduced into the oral cavity of a subject, who swirls it around for a specified period of time and then expels it. The subject then rinses his or her mouth with an aliquot of distilled water or buffer solution, and the expelled drug solution and rinse are combined and analyzed for drug content. The difference between the initial and final drug concentration in the solution is assumed to be the amount of drug taken up into the oral mucosa. 

Kurosaki Y, Hisaichi SI, Hong LZ, Nakayama T, Kimura T (1989b) Enhanced permeability of keratinized oral-mucosa to salicylic acid with 1 -dodecylazacycloheptan-2-one (Azone) In vitro studies in hamster cheek pouch. Int J Pharm 49 47-55... 

Lesch CA, Squier CA, Cruchley A, Williams DM, Speight P (1989) The permeability of human oral mucosa and skin to water. J Dent Res 68 1345-1349... 

Selvaratnam L, Cruchley AT, Navsaria H, Wertz PW, Hagi-Pavli EP, Leigh IM, Squier CA, Williams DM (2001) Permeability barrier properties of oral ker-atinocyte cultures A model of intact human oral mucosa. Oral Dis 7 252-258... 

Siegel IA (1984) Permeability of the oral mucosa. In Meyer J, Squier CA, Gerson SJ (eds.) The Structure and Function of Oral Mucosa. Pergamon Press, Oxford, pp 95-108... 

Siegel IA, Gordon HP (1985a) Effects of surfactants on the permeability of canine oral mucosa in vitro. Toxicol Lett 26 153-157... 

Siegel IA, Gordon HP (1985b) Surfactant-induced increases of permeability of rat oral mucosa to non-electrolytes in vivo. Arch Oral Biol 30 43 17... 

Siegel IA, Gordon HP (1986) Surfactant-induced alterations of permeability of rabbit oral mucosa in vitro. Exp Mol Path 44 132-137... 

Siegel IA, Hall SH, Stambaugh R (1971) Permeability of the oral mucosa. In Squier CA, Meyer J (eds.) Current Concepts of the Histology of Oral Mucosa. Thomas, Springfield, pp 274—286... 

Squier CA, Hall BK (1985a) The permeability of skin and oral mucosa to water and horseradish peroxidase as related to the thickness of the permeability barrier. J Invest Dermatol 84 176-179... 

Squier CA, Hall BK (1985b) In-vitro permeability of porcine oral mucosa after epithelial separation, stripping and hydration. Arch Oral Biol 30 485-491... 

Squier CA, Cox P, Wertz PW (1991a) Lipid content and water permeability of skin and oral mucosa. J Invest Dermatol 96 123-126... 

Wertz PW, Swartzendruber DC, Squier CA (1993) Regional variation in the structure and permeability of oral mucosa and skin. Adv Drug Del Rev 12 1-12... 

Zhang H, Robinson JR (1996) In vitro methods for measuring permeability of the oral mucosa. In Rathbone MJ (ed.), Oral Mucosal Drug Delivery. Marcel Dekker, New York, pp 85-100... 

Permeability coefficients typically range from lXlOMo2x 10 cm/s for oral mucosae [20]. The pathway of drug transport across oral mucosa may be studied by... 

Progestogens, alone or together with estrogen, cause an increase in the width and tortuosity of peripheral blood vessels in the oral mucosa, which become more susceptible to local irritants and show increased permeability (204). 

Wertz, P.W., et al. 1996. Biochemical basis of the permeability barrier in skin and oral mucosa. In Oral mucosal drug delivery, ed. M.J. Rathbone, 27. New York Marcel Dekker. 

Siegel, I. A. 1984. Permeability of the rat oral mucosa to organic solutes measured in vivo. Arch Oral Biol 29 13. 

Nicolazzo et al. [52] considered the use of the lipophilic skin penetration enhancers, octisalate and padimate (both used in sunscreens), in comparison to Azone on the buccal absorption of various drugs in vitro. They were found to have limited effect in enhancing the permeation of triamcinolone acetonide (although some increase in tissue uptake was proposed in some cases) relative to Azone, while reducing the penetration of estradiol and caffeine. One interesting report is that of the effect of capsaicin from capsicum, a commonly used food ingredient, which has been reported to enhance the permeability of sulfathiazole in human volunteers [53] presumably by a direct irritation effect on the mucosa. This raised an interesting issue of the effect of diet on oral mucosal permeability. 

In rats exposed for an intermediate duration to an unknown concentration of airborne white phosphorus from the furnace room of a phosphorus factory, an increase in permeability of capillary walls, lesions in the walls of blood vessels, and evidence of impaired microcirculation were observed in the mouth (Ruzuddinov and Rys-Uly 1986). Severe damage to the oral mucosa was also observed in these animals. No information regarding effects on the heart was located in the animal studies. 

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. 

Buccal administration offers certain unique advantages for drugs which cannot be easily or efficiently administered by the oral or intravenous route. However, transbuccal drug delivery has received relatively little attention and few well-controlled studies of buccal mucosa permeability have been conducted. 

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