Mucosal epithelial barrier

Neutra, M.R., Pringault, E. and Kraehenbuhl, J.P. (1996) Antigen sampling across epithelial barriers and induction of mucosal immune responses. Annual Review of Immunology 14, 275-300. 

The varying structure of the mucosal membrane in different parts of the oral cavity and the reduced permeation due to the barrier presented by the mucosal epithelial layers... 

The relative importance of many of the mediators is not precisely defined but they interact to produce mucosal oedema, mucus secretion and damage to the ciliated epithelium. Breaching of the protective epithelial barrier allows hyperreactivity to be maintained by bronchoconstrictor substances or by local axon reflexes through exposed nerve fibres. Wheezing and breathlessness result. The bronchial changes also obstruct access of inhaled drug to the periphery, which is why they can fail to give full relief. 

Lencer, W.L, 2001. Microbes and microbial toxins paradigms for microbial-mucosal interactions V cholera invasion of the intestinal epithelial barrier by a stably folded protein toxin. Am. J. Physiol. Gastrointest. Liver Physiol., 280, pp. G781-G786. 

Movement of penetrants across the mucous membranes is by diffusion. At steady state, the amount of a substance crossing the tissue per unit of time is constant and the permeability coefficients are not influenced by the concentration of the solutions or the direction of nonelectrolyte transfer. As in the epidermis of the skin, the pathways of permeation through the epithelial barriers are intercellular rather than intracellular. The permeability can be enhanced by the use surfactants such as sodium lauryl sulfate (a cationic surfactant). An unsaturated fatty acid, oleic acid, in a propylene glycol vehicle can act as a penetration enhancer for diffusion of propranolol through the porcine buccal mucosa in vitro. Delivery of biopharmaceuticals across mucosal surfaces may offer several advantages over injection techniqnes, which include the following ... 

Different mucosal surfaces differ in permeabihty. The permeability of nasal, rectal, and vaginal membranes from the rabbit was determined when nasa] vaginal rectal maunitol and Fnasal rectal vaginal progesterone [32], Permeability was assessed using electrical resistance and the permeability of epithelial barriers to a water-soluble fluorescent dye, 6-carboxyfluorescein. The rank order of permeabilities was intestinal nasal > bronchial > tracheal > vaginal > rectal > corneal > buccal > skin [33]. 

Cario E, Gerken G, Podolsky DK. Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function. Gastroenterology. 2007 132(4) 1359—1374. 

Inhibition of prostaglandin synthesis is the shared property which defines nonsteroidal anti-inflammatory drugs. It leads to impairment of prostaglandin-dependent mucosal defence mechanisms, including gastric mucosal blood flow, and mucus and bicarbonate secretion [7]. As a consequence, superficial breaches of the epithelial barrier, which can be prevented by exogenous prostaglandins, develop [8]. 

The paracellular route is probably less significant in the transport of nanospheres as compared to the transcellular route Tlie tight junctions in between the cells may not allow nanospheres to cross the intestinal epithelial barrier via paracellular route. The transcellular route could allow a restricted passage of the nanospheres across the intestinal mucosal layer because of their moderate size range. In a tissue culture model using Caco-2 (enterocytes) cell monolayers, we have demonstrated transport of PLGA nanospheres across the cells. 

Mucus is produced by the mucus neck cells and by the surface epithelial cells of the stomach wall. A thick layer of mucus adheres to the wall of the stomach, forming the gastric mucosal barrier. The function of this barrier is to protect the gastric mucosa from injury — specifically, from the corrosive actions of HCl and pepsin. Together with bicarbonate ion released into the lumen of the stomach, mucus neutralizes the acid and maintains the mucosal surface at a nearly neutral pH. 

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... 

A recent study, however, has shown that aminopeptidase activity is present on the surface of porcine buccal mucosa, and that various aminopeptidase inhibitors, including amastatin and sodium deoxycholate, reduce the mucosal surface degradation of the aminopeptidase substrate, leucine-enkephalin [149], Since the peptidases are present on the surface of the buccal mucosa, they may act as a significant barrier to the permeability of compounds which are substrates for the enzyme. In addition to proteolytic enzymes, there exist some esterases, oxidases, and reductases originating from buccal epithelial cells, as well as phosphatases and carbohydrases present in saliva [154], all of which may potentially be involved in the metabolism of topically applied compounds. 

The barriers of the eye differ from that of skin in dimensions and mucosal organization there are epithelial cel-Inlar barriers made of lipid layers on the eye and dry snrfaces made of proteins in the stratihed snrfaces of the skin. Skin is protected by a superficial outer fatty hhn, the stratum comeum, and covered by a thick layer of cells, the basal cellnlar layer. Thanks to these thick layers, skin has a high resistance to initial diffusion of aqueous fluids and less resistance to lipophilic solvents and to acids. The initial chemical cracking of the lipid layer allows fluids to invade deeper layers of the skin. The basal cell layer and the hair follicles contain stem cells capable of epithelial regeneration. 

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