Peptide physiochemical properties

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. 

Having physiochemical properties that improve probability of success in drug development by addressing issues of absorption and bioavailability including the filtering out of chemically reactive functional groups and peptides, compliance with ROF, etc. ... 

Rickard, C., Strohl, M. M., and Nielsen, R. G. (19 91) Correlation of electrophoretic mobilities from capillary electrophoresis with physiochemical properties of proteins and peptides. Anal. Biochem. 197, 197-207. 

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