Mucosal delivery

Veillard MM, Longer MA, Martens TW, and Robinson JR (1987) Preliminary studies of oral mucosal delivery of peptide drugs. J. Control. Rel. 6 123-131. 

Since the uptake of particles in nasal epithelial tissue is known to be mostly mediated by M cells, nasal administration has been investigated as a noninva-sive delivery of vaccines [37], However, since the uptake of naked DNA by endocytocis is limited, use of either nanoparticles as mucosal delivery systems [37] or hypotonic shock [38] is reported for the efficient transfection of gene and vaccine into the nasal epithelium. It was also reported that polypeptides and polypeptide-coated nanospheres (diameter about 500 nm) are transported through endocytic process in rat M cells [39],... 

Many factors were considered at the outset of the program in mucosal delivery systems and more specifically in the contraceptive and antiviral area, including ... 

Factors Affecting Systemic Oral Mucosal Delivery... 

IgG responses in mice, suggesting that this VLP composed of HBsAg is an excellent system for epitope presentation and mucosal delivery. 

Liposomes (see Chapter 9) have been used to deliver vaccines and have been observed to have immunostimulant activity. When administered orally liposomes with encapsulated antigens have been claimed to provide protection from the gastric proteolytic enzymes. Liposomes also have potential as mucosal delivery systems... 

Clark, M.A., B.H. Hirst, and M.A. Jepson. 2000. Lectin-mediated mucosal delivery of drugs and microparticles. Adv Drug Deliv Rev 43 207. 

O Hagan, D.T. 1998. Microparticles and polymers for the mucosal delivery of vaccines. Adv Drug Deliv Rev 34 305. 

The nonperoral mucosal delivery routes such as buccal, nasal, and vaginal sites offer barriers to drug molecules similar to that of the peroral route. Drugs delivered via these routes have to be small (<300 Da), lipophilic in nature, and with low dosage regimen requirements. The different approaches used to deliver drugs across these mucosae include the use of enzyme inhibitors, penetration enhancers, bioadhesive patches, prodrugs, liposomes, and solubility modifiers.96,106,130... 

Products formulated for mucosal delivery are now thought to contribute less than 5% of the total advanced drag delivery market, but wider utilisation of the mucosal route, now being researched by companies such as Theratech, 3M and Nomen, may eventually create a market worth over 300 billion. 

Drug moieties absorbed via the oral epithelium are delivered directly into the blood, avoiding first-pass metabolism effects of the hver and gut wall. Thus oral mucosal delivery may be particularly attractive for the delivery of enzymatically labile drugs such as therapeutic peptides and proteins. 

Hu, K. F., Elvander, M., Merza, M., Akerblom, L., BrAndenburg, A., and Morein, B. (1998), The immunostimulatory complex (ISCOM) is an efficient mucosal delivery system for respiratory syncytial virus (RSV) envelope antigens inducing high local and systemic antibody responses, Clin. Exp. Immunol., 113, 235-243. 

Bastein, N.,Trudel, M., and Simard, C. (1999), Complete protection of mice from respiratory syncytial virus infection following mucosal delivery of synthetic peptide vaccines, Vaccine, 17, 832-836. 

Davis, S. S. (2005), The use of soluble polymers and polymer microparticles to provide improved vaccine responses after parenteral and mucosal delivery, Vaccine, 24, Suppl. 2, S7-S10. 

Bowen, J. Alpar, H. Phillpotts, R. Brown, M. Mucosal delivery of herpes simplex virus vaccine. Research Virol. 1992, 143, 269-278. 

FACTORS AFFECTING SYSTEMIC ORAL MUCOSAL DELIVERY... 

Despite the fact that many such absorption-enhancing agents have been tried in mucosal delivery as well as in nasal delivery, only sodium caprate used in rectal suppositories of antibiotics has gained regulatory approval as an additive with absorption-enhancement activity.f Because most other compounds are not approved for mucosal application in the Pharmaco-peiae in many countries, specialized attention must be paid to putting these additives into practical use. For example, bile salts have been recognized as safe and... 

The synthesis of potent peptide analogues is also a commonly used strategy for mucosal delivery, with aims of increased stability of enzymatic degradation and increased lipophilicity. Several standard approaches include replacing typical amino acids with their corresponding o-amino acids, derivatizing the N-terminus or C-terminus, and cyclization. Several successful examples are metkephamid, desmopressin, and a few LHRH agonists. ... 

Senel S, Ikinci G, Kas S, et al. Chitosan films and hydrogels of chlorhexidine gluconate for oral mucosal delivery. Int ] Pharm 2000 193 197-203. 

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