Mucosal drug delivery

Oral Mucosal Drug Delivery, edited by Michael J. Rathbone... 

Structural specificity of mucosal-cell transport and metabolism of peptide drugs implication for oral peptide drug delivery. Pharm. Res. 1992, 9, 969-978. 

Hoogstraate, J., Benes, J., Burgaud, S., Horriere, F., Seyler, I., Oral trans-mucosal drug delivery, in Drug Delivery and Targeting. Hillery, A. M., Lloyd, A. W., Swarbrick, J. (eds), Taylor Francis, London, 2001, pp. 186-206. 

Wu et al. (2000) showed the formation of self-assembled nanoparticles of P(SA -block-EG) in an aqueous environment and studied their degradation as a function of pH and temperature. Fu et al. (2002) repeated the synthesis of P(SA-Wock-EG) and studied the morphology and erosion kinetics of microspheres which they propose as vehicles for mucosal drug delivery. 

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... 

Table taken from Squier et at. 1996 [125]. Copyright (1996) From Oral Mucosal Drug Delivery, by Michael J. Rathbone (Ed.). Reproduced by permission of Routledge/Taylor Francis Group, LLC. 

Squier CA, Wertz PW (1996) Structure and function of the oral mucosa and implications for drug delivery. In Rathbone MJ (ed.), Oral Mucosal Drug Delivery. Marcel Dekker, New York, pp 1-26... 

Although this section deals mainly with the advantages of excised tissues with respect to nasal drug delivery studies, it is important to highlight some important attributes of nasal in situ perfusion model. Although this method does not provide data on systemic absorption, it enables study of the interactions of nasal mucosal enzymes, peptide substrates, and metabolic inhibitors and their implications for nasal drug absorption [13], It also enables the rate of nasal drug absorption to be determined. 

Zhang H, Zhang J, and Streisand JB (2002) Oral mucosal drug delivery Clinical pharmacokinetics and therapeutic applications. Clin. Pharmacokinet. 41 661-680. 

Noninvasive drug delivery may require the administration of the drug delivery system (DDS) at an epithelium as a suitable site of absorption of the active compormd. Such regions are usually called mucosae. In the human body several mucosal sites can be identified, the one mostly used for administration and absorption of therapeutics being the gastrointestinal route. In order to increase the residence time at these absorption sites, a so-called mucoadhesive delivery system has to be used. Generally, these systems consist of one or more types of hydrogels. 

The failure in increasing residence time of mucoadhesive systems in the human intestinal tract has led scientists to the evaluation of multifunctional mucoadhesive polymers. Research in the area of mucoadhesive drug delivery systems has shed light on other properties of some of the mucoadhesive polymers. One important class of mucoadhesive polymers, poly(acrylic acid) derivatives, has been identified as potent inhibitors of proteolytic enzymes [72-74]. The interaction between various types of mucoadhesive polymers and epithelial cells has a direct influence on the permeability of mucosal epithelia by means of changing the gating properties of the tight jrmctions. More than being only adhesives, some mucoadhesive polymers can therefore be considered as a novel class of multifunctional macromolecules with a number of desirable properties for their use as delivery adjuvants [72,75]. 

Squier, C.A., and Wertz, P.W., Structure and Function of the Oral Mucosa and Implications for Drug Delivery. In Oral Mucosal Drug Delivery (M.J. Rathbone, ed.), Marcel Dekker, Inc., New York, 1996, pp. 1-26. 

Needleman, I.G., Martin, G.P., and Smales, F.C., Characterisation of bioadhesives for periodontal and oral mucosal drug delivery, J. Clin. PeriodontoL, 25 74-82 (1998). 

A buccal drug delivery system is applied to a specific area on the buccal membrane. Moreover, the delivery system ean be designed to be unidirectional in drug release so that it can be protected from the loeal environment of the oral cavity. It also permits the inclusion of a permeation enhancer/protease inhibitor or pH modifier in the formulation to modulate the membrane or the tablet-mucosal environment at that particular application site. While the irritation is limited to the well-defined area, the systemic toxicity of these enhancers/inhibitors and modifiers can be reduced. The buccal mucosa is well suited for this type of modification as it is less prone to irreversible damage [9]. In the event of drug toxicity, delivery can be terminated promptly by removal of the dosage form. 

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