Polypeptides nasal delivery

A number of other peptide molecules are currently being explored for delivery via inhalation (6). Very recently, a much smaller peptide (leuprolide, about 9 amino acid residues) has been delivered by metered dose inhaler (MDI) in a characterized fashion to humans (7). This work revealed that about 50% of a dose deposited in the lung could be bioavailable. This value is much greater than those reported for nasal bioavailabilities of this and similar molecules (8). These results, and ours in the rat lung (9), imply that inhalation administration of some peptide and polypeptide molecules is perfectly feasible. 

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],... 

Since its discovery, isolation, and purification in the early twentieth century, insulin has been administered to diabetic patients exclusively by injection until the recent introduction of inhaled insulin. Insulin possesses certain physiochemical properties that contribute to its limited absorption from the gastrointestinal tract, and requires subcutaneous injection to achieve clinically relevant bioavailability. With a molecular size of 5.7 kDa, insulin is a moderately sized polypeptide composed of two distinct peptide chains designated the A chain (21 amino acid residues) and the B chain (30 amino acid residues) and joined by two disulfide bonds. Like all polypeptides, insulin is a charged molecule that cannot easily penetrate the phospholipid membrane of the epithelial cells that line the nasal cavity. Furthermore, insulin monomers self-associate into hexameric units with a molecular mass greater than 30 kDa, which can further limit its passive absorption. Despite these constraints, successful delivery of insulin via the nasal route has been reported in humans and animals when an absorption enhancer was added to the formulation. 

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