Buccal mucosa permeability barrier

Keywords Buccal mucosa Permeability barrier Passive diffusion Excised tissue Nonkeratinized epithelium Diffusion chamber... 

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. 

Because of the possible effects of active and carrier-mediated processes and metabolic biotransformation, the issue of tissue viability is important for in vitro buccal mucosal experiments. The barrier nature of the buccal mucosa resides in the upper layers of the epithelium, where unlike in the stratum corneum, the cells contain a variety of functional organelles [119, 122, 125, 150], and so tissue viability may be an important component of the barrier function of the tissue. Various methods have been employed to assess the viability of excised buccal mucosa, including measurement of biochemical markers, microscopic methods, and linearity of transport data [42], While biochemical methods, including measurement of adenosine 5 -triphosphate (ATP) levels and utilization of glucose, provide information on the metabolic activity of the tissue, this does not necessarily relate to the barrier function of the tissue. In excised rabbit buccal mucosa, levels of ATP were measured and found to decline by 40% in 6 h, and this correlated well with transmission electron microscopic evaluation of the tissue (intact superficial cells) [32], In addition, the permeability of a model peptide was unaltered up to 6 h postmortem, but at 8 h, a significant change in permeability was observed [32], These investigators therefore claimed that excised rabbit buccal mucosa could be used for diffusion studies for 6 h. 

Recently it has been claimed that the tissue can be considered viable if the drug permeability does not change over the course of the experiment, and thus the actual permeability experiments themselves may provide insight into the viability of the tissue [109, 157], This method was employed in permeation experiments using porcine buccal mucosa, where the permeability of compounds was assessed in two consecutive permeability experiments to ensure the nature of the barrier was not compromised [111, 112]. While this demonstrates that the barrier nature of the tissue was unaltered between the permeation experiments, the tissue may have already undergone tissue death in the time between the excision and the commencement of the initial permeation experiment, and thus the permeability rate obtained in vitro may not be representative of the in vivo situation. Therefore, more studies assessing the dependence of the barrier nature of the buccal mucosa on tissue viability are... 

TR146 cell culture. With the development of tissue culture techniques, it is anticipated that various cell culture models may be developed with similar morphological and barrier properties to normal intact buccal mucosa. Such models may be very useful in assessing the buccal permeability and metabolism of many compounds. 

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. 

Extent of Damage to Mucosal Cells. Permeation enhancement implies possible alteration of the protective permeability barrier either by 1) an increase in the fludity of intercellular lipids (relatively non-toxic) and/ or 2) extraction of intercellular lipids or denaturation of cellular proteins (much more damaging/toxic). Therefore, it is imperative that the permeation enhancer 1) exert a reversible effect 2) not be systemically absorbed and 3) not cause cumulative toxicity or permanent changes in the barrier properties. Application of up to 1% sodium lauryl sulfate or cetylpyridinium chloride to the ventral surface of the tongue of dogs resulted in desquamation, widening and separation of keratin.f The buccal mucosa of rabbits treated with... 

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 ... 

The human buccal mucosae of the oral cavity, i.e., the buccal and the sublingual epithelia, offer a robust and easily accessible area for systemic delivery and the advantage of low enzymatic activity (Lee et al., 1987 Yamamoto et al, 1990). Unfortunately, the multilayered buccal barrier is relatively thick and dense, and proteinaceous substances are not readily absorbed via this route. Thus, permeability of insulin via this route has been calculated to be 12 orders of magnitude less than via the nasal route (Harris and Robinson, 1990). 

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... 

---