Mucosal routes of delivery

Advantages of the oral mucosal route of delivery include its capacity to bypass all the limitations associated with the oral route, ease of administration, relatively low content of enzymes, and adequate vascular drainage. As described in the following sections, most of the limitations of the oral mucosa epithelium arise from its stratified nature and its intercellular content characteristics. Nonetheless, due to its direct connection to systemic circulation, delivery systems could potentially be formulated to show either bolus-like or controlled release profiles for specific therapeutic needs. Polymers used in the development of such delivery systems play a major role in the release profile, permeation enhancement, and the localization of the active in the vicinity of the absorbing mucosa. Among the various uses of polymers in delivery systems, their mucoadhesive nature is the most prominent application in the oral mucosal route and is the main focus of this entry. After describing the physiological considerations in the oral cavity mucosa, this entry will review the literature pertinent to the use of polymers in delivery systems for the oral mucosal route. 

The success of vaccination depends primarily on the method of presenting the antigen to the host immune system. Antigens have usually been delivered by parenteral (such as intravenous, intramuscular, intraperito-neal, intradermal, and subcutaneous) administration, but recent studies have shown that other routes of delivery such as intranasal, oral, and transdermal delivery have also been effective. In some cases, vaccination through mucosal routes resulted in better responses in IgA production. Because non-parenteral vaccine delivery presents many obvious advantages, numerous attempts have been made on the development of non-parenteral delivery of vaccines. 

The oral route is undoubtedly the most widely investigated alternative administration route however, it presents major concerns in the delivery of macromolecular actives. The gastrointestinal route can promote degradation in the stomach due to the acidic gastric pH. The intestine has issues arising from the presence of proteolytic enzymes and insufficient permeation toward these actives, all of which result in limited bioavailability. Therefore, other routes of delivery have been investigated and the oral mucosal route presents a convenient alternative. 

Shao, Z., Li, Y., and Mitra, A. K., 1994b, Cyclodextrins as mucosal absorption promotors of insulin. III. Pulmonary route of delivery, r. J. Pharm. Biopharm. 40 283-288. 

A micellar phase is formed in the intestinal lumen when the bile salt concentration exceeds the critical micellar concentration (approximately 3-4 mM). This concentration of bile salts is usually exceeded during normal digestion. Mixed micelles contain bile salts, fatty acids, monoglycerides, cholesterol, and other lipid-soluble molecules (including fat-soluble vitamins) and are considered to be the major route of delivery of the products of fat digestion to the absorptive mucosal cell. Other nonmicellar phases may coexist in the intestinal lumen with the micellar phase these include an oil phase and a viscous isotropic phase. 

Dendrimers have been employed in other routes of delivery such as rectal, vaginal, and mucosal. VivageB (Starpharma, Melbourne, Australia) is a dendrimer-based microgel in clinical trials for the prevention of sexually transmitted infections. Iontophoresis is another method to enhance the penetration of dendrimer-based therapeutics using a weak electric field. 

Yamamoto A, Hayakawa E, Lee VH (1990) Insulin and proinsulin proteolysis in mucosal homogenates of the albino rabbit Implications in peptide delivery from nonoral routes. Life Sci 47 2465-2474... 

Mestecky, J., Michalek, S. M., Moldoveanu, Z., and Russell, M. W. (1997). Routes of immunization and antigen delivery systems for optimal mucosal immune responses in humans. Behring Inst. Mitt. 98, 33-43. 

The induction of an immune response by various mucosal routes is an important approach for the control of mucosally acquired infections. The apparent linked nature of the mucosal immune system enables the delivery of an antigen to any mucosal surface to have the secondary effect of potentially inducing immunity at others. Induction of a combination of systemic and secretory immune responses can be determined by the nature of the antigen, the route of administration, and the delivery system utilized. For example, traditional parenteral vaccines primarily induce IgM and IgG responses, whereas mucosal vaccination can elicit both IgG and secretory IgA responses (Corthesy, 2007). 

In comparison to the skin, the buccal mucosa offers higher permeability and faster onset of drug delivery, whereas the key features which help it score over the other mucosal route, the nasal delivery system, include robustness, ease of use, and avoidance of drug metabolism and degradation. The buccal mucosa and the skin have similar structures with multiple cell layers at different degrees of maturation. The buccal mucosa, however, lacks the intercellular lamellar bilayer structure found in the stratum corneum, and hence is more permeable. An additional factor contributing to the enhanced permeability is the rich blood supply in the... 

Membranous epithelial M cells are a part of the organized mucosa-associated lymphoid tissue (O-MALT). These cells are specialized for antigen sampling. Also, they are exploited as a route of invasion by several pathogens.39 M cells are concentrated in follicle-associated epithelial (FAE) tissue called Peyer s patches in the small intestine. As M cells carry out endocytotic transport, they can be potential vehicles for mucosal drug and vaccine delivery. 

Buccal mucosal permeability also varies with the anatomical site for example, keratinized sites of the oral cavity hinder the permeation of hydrophilic molecules.96 Therefore, it is important to consider these factors in selecting the transmucosal route for drug delivery in the oral cavity. A limited surface area (100 to 170 cm2) and the need to mask taste for bitter drugs are some of the drawbacks associated with this route of drug delivery. 

Considering patient acceptability and ease of administration, there is no doubt that oral administration is the most favored route, even if there have been reports on successful delivery of macromolecular drugs across nonperoral mucosal routes.6 7 Despite such advantages in oral administration, various barriers are encountered in the gastrointestinal (GI) tract that should be surmounted in order to gain sufficient bioavailability of... 

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