Peptides nasal drug delivery

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. 

Peptide YY (PYY) is a peptide hormone produced by L-cells in the intestinal tract after eating. It appears to act centrally to diminish appetite. It may serve normally to produce a sense of satiety. Diminished PYY production would be expected to cause increase in appetite and increased food intake. Hence, a biologically active PYY derivative, PYY 3-36, is under investigation as a potential agent to treat obesity and type 2 diabetes. A nasal PYY 3-36 product, if developed, would be an attractive alternative to injected PYY 3-36 because of the rapid and direct nose-to-brain drug transport that occurs following nasal drug delivery. 

Ilium, L., N.F. Farraj, and S.S. Davis. 1994. Chitosan as a novel nasal drug delivery system for peptide drugs. Pharm Res 11 1186. 

Drug delivery via the nasal route offers a number of advantages, the most important of which is the possibility of needle-free treatment. It also means that—in addition to the newly developed peptide- and protein-based drugs—this method is also suitable for a wide variety and perhaps most of the drugs that are currently in use. However, it is not only convenience that sets nasal drug delivery apart This method also provides a rapid onset of action and high bioavailability. 

Merkus, P. (2003),Transport of non-peptide drugs from the nose to the CSF, paper presented at the Nasal Drug Delivery Meeting, Management Forum, London, Mar. 24-25. 

Microspheres can be used as nasal drug delivery systems for systemic absorption of peptides and proteins. 

Peptide and protein nasal drug delivery have challenges related to their unique physical and chemical properties and comprise issues of chemical stability, loss due to physical absorption (especially for low-dose/high-potency molecules) and self-aggregation. The two key factors for nasal delivery of peptides are molecular mass and lipophilicity. The transitional area between a predicted good absorption and a predicted increasing difficulty of absorption is a molecular mass of about 1,000 (McMartin et al. 1987). Complete absorption of a peptide, by... 

Ilium, L., Bioadhesive Formulations for Nasal Peptide Delivery. In Bioadhesive Drug Delivery Systems (E. Mathiowitz, D.E. Chiekering, III, and C.-M. Lehr, eds.), Marcel Dekker, Inc., New York, 1999, pp. 507-539. 

A host of bioadhesive controlled release systems have been proposed in recent years. Among the most commonly studied applications of bioadhesive materials is the area of buccal controlled delivery [408], The buccal delivery of small peptides from bioadhesive polymers was studied by Bodde and coworkers [409], and a wide range of compositions based on poly(butyl acrylate) and/or poly(acrylic acid) gave satisfactory performance. Bioadhesive poly(acrylic add)-based formulations have also been used for oral applications [402,410] for the sustained delivery of chlorothiazide [410] and for a thin bioadhesive patch for treatment of gingivitis and periodontal disease [411]. Other bioadhesive applications of polyelectrolytes include materials for ophthalmic vehicles [412,413], and systems for oral [410,414,415-419], rectal [420,421] vaginal [422] and nasal [423] drug delivery. 

Arnold, J.J., et al. 2004. Correlation of tetradecylmaltoside induced increases in nasal peptide drug delivery with morphological changes in nasal epithelial cells. J Pharm Sci 93 2205. 

Due to the lack of activity after oral administration for most peptides and proteins, administration by injection or infusion - that is, by intravenous (IV), subcutaneous (SC), or intramuscular (IM) administration - is frequently the preferred route of delivery for these drug products. In addition, other non-oral administration pathways have been utilized, including nasal, buccal, rectal, vaginal, transder-mal, ocular, or pulmonary drug delivery. Some of these delivery pathways will be discussed in the following sections in the order of the increasing biopharmaceutic challenges to obtain adequate systemic exposure. 

Ilium, L. (1999), Bioadhesive formulations for nasal peptide delivery, in Mathiowitz, E., Chickering, D. E., and Lehr, C.-M., Eds., Bioadhesive Drug Delivery Systems, Fundamentals, Novel Approaches and Development, Marcel Dekker, New York, pp. 507-539. 

Dry powder formulations for nasal delivery of peptides and proteins have been investigated for the first time by Nagai and others [38], Since then, much research work has been done on dry powders containing bioadhesive polymers for nasal drug administration. The bioavailability and duration of action of drugs administered by the nasal route are increased by the use of the principle of mucoadhesion and dry powder formulations. Research work on dry powder formulation containing bioadhesive polymers is summarized in Table 1. 

---