Peptide oral delivery

M Asgharnejad, GL Amidon. Improved oral delivery via the peptide transport A dipeptide prodrug of L-amethyldopa. Pharm Res 9 5-248, 1992. 

During the past 10 years, one of the most exciting developments in the oral peptide drug delivery was the identification of PEPT1. This is a significant finding because this carrier protein is known to play a critical role in the absorption of... 

Lipka, E., J. Crison, and G. L. Amidon. Transmembrane transport of peptide type compounds prospects for oral delivery. J. Control. Release 1996, 39, 121-129. 

Structural specificity of mucosal-cell transport and metabolism of peptide drugs implication for oral peptide drug delivery. Pharm. Res. 1992, 9, 969-978. 

Jung, T., Kamm, W., Breitenbach, A., Kaiserling, E., Xiao, J.X., Kissel, T., Biodegradable nanoparticles for oral delivery of peptides Is there a role for polymers to affect mucosal uptake Eur J Pharm Biopharm 50, 147-160 (2000). 

M. K. Marschiitz, A. Bernkop-Schniirch, Oral Peptide Drug Delivery Polymer-Inhibitor Conjugates Protecting Insulin from Enzymatic Degradation in vitro, Biomaterials 2000, 21, 1499-1507. 

Saffran, M., Kumar, G.S., Neckers, D.C., Pena, J., Jones, R.H., and Field, B., Biodegradable azopolymer coating for oral delivery of peptide drugs, Biochem. Soc. Trans., 18 752-754 (1990). 

Besides parenteral application of microspheres and nanoparticles for cell selective delivery of drugs, they have more recently been studied for their application in oral delivery of peptides and peptidomimetics [30]. Immunological tolerance induction against beta-lac-toglobulin could be achieved by application of this protein in a poly-lactic-glycolide microsphere formulation [31]. 

Joseph, J.W., 1. Kalitsky, S. St-Pierre, and P.L. Brubaker, Oral delivery of glucagonlike peptide-1 in a modified polymer preparation normalizes basal glycaemia in diabetic db/db mice. Diabetologia, 2000. 43(10) 1319-28. 

The degradation rate can be controlled using acidic and basic excipients acidic excipients increase the degradation rates and facilitate a zero-order release rate over a 2-week period (Sparer et al. 1984). Basic additives increase the degradation time of the polymers and create a polymer that degrades specifically at the surface (Heller 1985). By careful choice of the excipient added, the degradation rate can be closely controlled. No experiments have shown the use of these polymers with proteins or peptides. This is not, however, indicative of the fact that these polymers are not compatible with proteins or peptides, but they are probably not the most appropriate polymeric carrier for oral delivery of biomacromolecules. 

Despite the fact that these polymers show delivery patterns comparable to gastric transit, there have not been any substantial reports of oral delivery of peptides or proteins based on this type of polymer. Further investigations into this polymer may... 

With all of the advances in polymer science and conjugation technology, many methods have been developed to increase the feasibility of oral peptide and protein delivery. There is still no single mechanism that can be used to protect a protein or peptide from degradation and increasing oral availability, but with the multitude of new methods for allowing a protein to negotiate natural barriers, oral delivery of any systemically active protein is a definite possibility at some point in the future. 

Bemkop-Schntirch, A. and Scerbe-Saiko, A. (1998). Synthesis and in vitro evaluation of chitosan/EDTA/protease inhibitor conjugates which might be useful in oral delivery of peptides and proteins. Pharmaceut. Res., 15, 263-369. 

Geary, R.S., and H.W. Schlameus. 1993. Vancomycin and insulin used as models for oral delivery of peptides. J Control Release 23 65. 

Yamamoto, A., E. Hayakawa, and V.H.L. Lee. 1990. Insulin and proinsulin proteolysis in mucosal homogenates of the albino rabbit Implications in peptide drug delivery from non-oral routes. Life Sci 47 2465. 

Mahato RI, Narang AS, Thoma L, Miller DD. Emerging trends in oral delivery of peptide and protein drugs. Crit Rev Ther Drue Carrier Syst. 2003 20 153-214. 

Fasano, A. Innovative strategies for the oral delivery of drugs and peptides. Trends Biotechnol. 16 152-157, 1998. 

Marschutz, M. K., and Bernkop-Schniirch, A. Oral peptide drug delivery Polymer-inhibitor conjugates protecting insulin from enzymatic degradation in vitro. Biomaterials 21 1499—1507, 2000. 

Iwanaga, K., Ono, S., Narioka, K., et al. Application of surface-coated liposomes for oral delivery of peptide effects of coating the liposome s surface on the GI transit of insulin. -/. Pharm. Sci. 88 248—252, 1999. 

In addition to their usefulness in the enhancement of oral bioavailability of lipophilic drugs, microemulsion formulations have found considerable application as potential delivery systems for peptides whose delivery is often limited by poor GI permeability. W/O microemulsions provide a convenient means of delivery of both permeability-enhancing lipids and water-soluble peptides. The GI permeability-enhancing effects of lipids and their use in the delivery of highly water-soluble compounds are reviewed elsewhere [18, 56, 59],... 

Most peptides and proteins are currently formulated as parenteral formulations because of their poor oral bioavailability. Nevertheless, oral delivery of peptides and proteins would be the preferred route of administration if bioavailability issues could be overcome, as it offers the advantages of convenient, pain-free administration. Although various factors such as permeability, chemical and metabolic stability and gastrointestinal transit time can affect the rate and extent of absorption of orally administered peptides and proteins, molecular size is generally considered the ultimate obstacle [36]. 

Several promising strategies have emerged from the intensive recent research efforts into the oral delivery of peptides and proteins [6, 36, 37]. Absorption enhancers may be used either to temporarily disrupt the intestinal barrier so that drug... 

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