Systemic Delivery of Peptides and Proteins

As mentioned above, the rectal route is very attractive for systemic delivery of peptide and protein drugs, but rectal administration of peptides often results in very low bioavailability due to not only poor membrane penetration characteristics (transport barrier) but also due to hydrolysis of peptides by digestive enzymes of the GI tract (enzymatic barrier). Of these two barriers, the latter is of greater importance for certain unstable small peptides, as these peptides, unless they have been degraded by various proteases, can be transported across the intestinal membrane. Therefore, the use of protease inhibitors is one of the most promising approaches to overcome the delivery problems of these peptides and proteins. Many compounds have been used as protease inhibitors for improving the stability of various peptides and proteins. These include aprotinin, trypsin inhibitors, bacitracin, puromycin, bestatin, and bile salts such as NaCC and are frequently used with absorption enhancers for improvement in rectal absorption. 

Sayani, A.P., and Y.W. Chien. 1996. Systemic delivery of peptides and proteins across absorptive mucosae. Crit Rev Ther Drug Carrier Syst 13 85. 

Several products for the systemic delivery of peptide and protein drugs via the nasal route are currently available in the marketplace, as shown in Table 1. Most of these peptides, with molecular weights ranging from 1000 to 3400, have been conventionally used as injection forms. 

The eye is not, of course, a general route for the administration of drugs to the body, although it has been explored for the systemic delivery of peptides and proteins such as insulin. It is considered here because absorption of drugs does occur from medication applied to the eye, producing sometimes toxic systemic effects, although often the desired local effect is on the eye or its component... 

Pulmonary systemic delivery of peptides and proteins has recently been reviewed by Patton and Platz (1992), Adjei and Gupta (1994), Byron and Patton (1994), and Wall (1995). 

J. S. Patton and R. M. Platz, Routes of drug delivery case studies (2) pulmonary delivery of peptides and proteins for systemic action, Adv. Drug Deliv. Rev, 8, 179 (1992). 

Garcia-Contreras L, Smyth HDC. Dry-powder and liquid spray systems for inhaled delivery of peptide and proteins. Am J Drug Delivery 2005 3(1) 29—45. 

Different drug delivery systems have been proposed for vaginal delivery of peptides and proteins. The first one was a mucoadhesive gel based on polyacrylic acid intended for vaginal administration of insulin [96]. More recently, microparticulate systems such as starch and hyaluronan ester (HYAFF) microspheres have been proposed for vaginal delivery of insulin... 

Ability to maintain a constant drug input in the colon for up to 24 h or to deliver drug over an interval as short as 4 h Oral delivery of peptides and proteins. The system can be used to study colonic absorption in humans prior to development of colon-specific delivery systems. 

Wall, D.A. Smith, P.L. Inhalation therapy for growth hormone deficiency. In Inhalation Delivery of Therapeutic Peptides and Proteins Adjei, A.L., Gupta, P.R., Eds. Marcel Dekker, Inc. New York, 1997 453-469, Ch. 16. Patton, J.S. Platz, R.M. Routes of dehvery case studies (2) pulmonary delivery of peptides and proteins for systemic action. Adv. Drug Deh. Rev. 1992, 8, 179-186. 

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