Mucosal administration

Because most proteins are susceptible to protease degradation and denaturation in biologic fluids, most biopharmaceuticals must be administered by intravenous, intramuscular, or subcutaneous injection (see Table 5.5). High concentrations of proteases are found in the gastrointestinal tract, nasal mucosa, bronchioles, and alveoli, which severely limit the bioavailability of protein pharmaceuticals after oral, intranasal, and inhalation administration. Diffusional barriers to the passage of relatively large macromolecules preclude transdermal and mucosal administration of protein pharmaceuticals. Research is under way to develop methods that will protect protein drugs from proteolysis and improve transmembrane diffusion. 

The net effect is that mucosal administration of a vaccine is an attractive and more effective alternative to parenteral administration which, in any case, tends to only provide systemic protection. 

From the variety of experimental studies it becomes obvious that mucosal administration is a powerful tool for modulating immune responses. Apart from the importance to test the effectiveness and the mechanisms of action of any allergen of interest as a potential antiallergic agent or tolerogen in animal models, prophylactic treatment strategies could be of interest in patients with a known risk to develop allergy. 

Yamamoto, A., et al. 2001. Absorption of water soluble compounds with different molecular weights and [ASU1.7]-eel calcitonin from various mucosal administration sites. J Control Release 76 363. 

BenMohamed, L., Belkaid, Y., Loing, E Brahimi, K Gras-Masse, H., and Druilhe, P. (2002) Systemic immune responses induced by mucosal administration of lipopeptides without adjuvant. Eur. J. Immunol. 32(8), 2274-2281. 

O Hagan, D.T. Recent advances in vaccine adjuvants for systemic and mucosal administration. J. Pharm. Pharmacol. 1997, 49, 1-10. 

Lately, the nasal route is receiving attention for the management of postoperative pain. Mucosal administration requires only a 1.1-1.5 times higher dose of fentanyl than the intravenous dose. ° For this new application field, called PCINA (patient-controlled-intranasal-analgesia), the pharmaceutical industry demands safety precautions of the delivery device, which can be fulfilled through implementation of intelligent microelectronic features. 

Shroff, K.E. Marcucci-Borges, L.A. de Bruin, S.J. Winter, L.A. Tiberio, L. Pachuk, C. Snyder, L.A. Satishchandran, C. Ciccarelli, R.B. Higgins, T.J. Induction of HSV-gD2 specific CD4(+) cells in peyer s patches and mucosal antibody responses in mice following DNA immunization by both parenteral and mucosal administration. Vaccine 1999,18, 222-230. 

Recently, plasmid DNA has been considered as a viable therapy to treat diseases like cystic fibrosis, Parkinson s, and diabetes (5,6). Further, DNA vaccines for mucosal administration (7) and intranasal inhalation (121) are currently being developed for a variety of diseases. These developments have increased the interest in developing plasmid DNA powders. PCA, a proven particle formation technology, has been applied to the production of plasmid DNA micropowders. Tservistas et al. (107) precipitated pSVp, a 6.9-kb plasmid, from an aqueous solution using isopropanol-modified SCF CO2... 

Because vaccines alone cannot be sufficiently taken up after mucosal administration, they need to be co-administered with penetration enhancers, adjuvants, or encapsulated in microparticles. Chitosan particles, powders, and solutions are promising candidates for mucosal vaccine delivery. The aspecific adjuvant activity of chitosans seems to be dependent on the deacetylation degree and the type of formulation. 

Many polysaccharides contain branched structures and are chemically modified by the addition of other molecules. Their monomeric or repeat units are often made up of more than one sugar molecule and, consequently, can be quite complex. They form protective capsules of some of the most virulent microorganisms, capsules that, nevertheless, carry information that activate mammalian defenses the immune, interferon, and properdin systems [9, 136]. They are found as key portions of the exoskeletons of insects and arthropods and cell walls of plants and microbes and perform as reserve foodstuffs and important components of intercellular, mucous secretions, synovial and ocular fluids, and blood serum in many organisms. Food Applications compiles recent data on the food applications of marine polysaccharides from such various sources as fishery products, microorganisms, seaweeds, microalgae, and corals [137, 138]. One of the applications of this biopolymer relates to a method for protecting against diseases induced by Streptococcus pneumoniae infections, which comprises mucosal administration of a S. pneumoniae capsular polysaccharide to a patient in need. 

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