Intranasal peptide delivery

A. S. Harris, Biopharmaceutical aspects of the intranasal administration of peptides, in Delivery Systems for Peptides (S. S. Davis, L. Ilium, and E. Tomlinson, eds.), Plenum Press, New York, 1986, p. 191. 

The presence of multiple FnBPs could possibly explain how S. pyogenes is able to colonize different host tissue and confer various tissue tropisms. The identification of fhe Sfbl adhesin has contributed to the recent development of vaccines composed of Sfbl-derived peptides conjugated to either the diphtheria toxoid or used with the Lipid Core Peptide (TCP) delivery system. These vaccines have been shovm to confer protective immunity to BALC/c mice when challenged intranasally with lethal doses of S. pyogenes (Olive et ah, 2007 Schulze et ah, 2006). 

Ilium, L., and A. N. Fisher. 1997. Intranasal delivery of peptides and proteins. Inhalation delivery of therapeutic peptides and proteins, edited by A. L. Adjei and P. K. Gupta. New York. Marcel Dekker, pp. 135-184. 

Ilium L, Fisher N. Intranasal delivery of peptides and proteins. In Adjei AL, Gupta PK, eds. Inhalation Delivery of Therapeutic Peptides and Proteins. New York Marcel Dekker, 1997 135-184. 

Antimicrobial and antiendotoxin cationic peptide, CM3, incorporated into liposomes was suggested for the aerosol delivery, and corresponding models describing its potential distribution in lungs of patients with different breathing patterns have been developed.Liposomes with calcitonin have been developed for intranasal delivery. Liposomal forms of the peptide antibiotic, polymyxin B, showed certain promise in different models.355-357... 

Maggio, E.T. 2005. Recent developments in intranasal drug delivery technology are creating new vistas for peptide and protein therapeutics. Drug Deliv Comp Report, Spring/Summer 34 37. 

These concerns largely preclude the utility of thermoplastic polymers as the primary choice of container closure system for protein and peptide therapeutics, although the formulation scientist should be aware of the potential advantages of these systems, such as the ease of manufacturability and their cost. These systems are also finding greater utility in intranasal and pulmonary delivery systems. 

Numerous papers have reported on the possible utility of nasal administration of a variety of compounds, including peptide and protein drugs. However, only a small number of products are of clinical use for intranasal systemic delivery, as mentioned earlier. Especially, most peptide and protein drugs show insufficient nasal bioavailability, which may be one of the reasons for difficulties in development. To improve the nasal absorption of peptide and protein drugs, several strategies classified as follows have been intensively investigated and discussed during the last two decades ... 

Sulfobutylether P-cyclodextrin can form noncovalent complexes with many types of compounds including small organic molecules, peptides, and proteins. It can also enhance their solubility and stability in water. The first application of sulfobutylether P-cyclodextrin was in injectable preparations it can also be used in oral solid and liquid dosage forms, and ophthalmic, inhalation, and intranasal formulations. Sulfobutylether P-cyclodextrin can function as an osmotic agent and/or a solubilizer for controlled-release delivery, and has antimicrobial preservative properties when present at sufficient concentrations. 

Only two antidiuretic peptides are available for clinical use in the United States (1) Vasopressin (synthetic 8-l-arginine vasopressin Pitressin) is available as a sterile aqueous solution it may be administered subcutaneously, intramuscularly, or intranasally. (2) Desmopressin acetate (synthetic l-deamino-8-D-arginine vasopressin DDAVP, others) is available as a sterile aqueous solution packaged for intravenous or subcutaneous injection, in a nasal solution for intranasal administration with either a nasal spray pump or rhinal tube delivery system, and in tablets for oral administration. The therapeutic uses of vasopressin and its congeners can be divided into two main categories according to the type of vasopressin receptor involved. 

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