Oral epithelium permeability

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. 

Squier CA (1973) The permeability of keratinized and nonkeratinized oral epithelium to horseradish peroxidase. J Ultrastruct Res 43 160-177... 

Squier, C. and Hopps, R. A study of the permeability barrier in epidermis and oral epithelium using horseradish peroxidase as a tracer in vitro. Br. J. Derm. 95 123-129, 1976. 

Vaginal Rings. Vaginal epithelium is readily permeable to contraceptive steroids. Since the vascular drainage of the vagina bypasses the Hver, this route of adrninistration potentially permits utilisation of dmgs that have low oral activity. 

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 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 main permeability barrier in the airways to blood pathway lies with the epithelium of the lung airway rather than the intersitium or endothelial lining of the capillaries. The epithelial permeability towards hydrophilic solutes is at least 10-fold lower than that of the endothelium. The epithelium of the lung is much more permeable than that of other mucosal routes. For example, less than 3% of an oral dose of sodium cromoglycate reaches the circulation whereas more than 70% is absorbed from the lung into the bloodstream after inhalation. 

The second major obstacle of the oral delivery of proteins is the low permeability of proteins in the intestinal epithelium. The uptake of proteins is mediated by passive diffusion across the enterocytes (transcellular diffusion), paracellular diffusion (through intercellular spaces) and mostly by transcytosis (facilitated by receptor-mediated endocytosis). Erodible microcapsules and nanoparticles were shown to be absorbed intact through the GI tract and have opened the pos-... 

Systemic bioavailability is the product of fraction of dose absorbed (/a), fraction of dose escaping gut metabolism (/g), and fraction of dose escaping first-pass metabolism (F ). Permeability class is based upon /a, which may be estimated either in vivo or in vitro by direct measurement of mass transfer across human intestinal epithelium. In vivo methods include (i) mass balance studies using unlabeled, stable-isotope labeled, or a radiolabeled drug substance (ii) oral bioavailability using a reference intravenous dose or (iii) intestinal perfusion studies either in humans or an acceptable animal model. Suitable in vitro methods involve the use of either excised human/animal intestinal tissues or cultured epithelial monolayers. All of these methods are deemed appropriate for drugs whose absorption is controlled by passive mechanisms. 

Orally administered corticosteroids are effective in the treatment of chronic bronchial asthma. The inhalation route has been widely used in attempts to avoid systemic side-effects, such as adrenal suppression, but evidence suggests that inhaled steroids are absorbed systemically to a significant extent. The respiratory tract epithelium has permeability characteristics similar to those of the classical biological membrane, so lipid-soluble compounds are absorbed more rapidly than lipid-insoluble molecules. Cortisone, hydrocortisone and dexamethasone are absorbed rapidly by a nonsaturable diffusion process from the lung, the half-time of absorption being of the order of 1-1.7 min. Quaternary ammonium compounds, hippurates and mannitol have absorption half-times, in contrast, of between 45 and 70 min. 

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