Drugs oral peptide

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... 

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

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. 

There are a number of problems associated with the use of peptides as drug molecules. Peptides are rapidly degraded by proteases and, therefore, their biological half lives are normally too short to be useful In a therapeutic sense. Most peptides exhibit more than one type of biological effect making lack of specificity a problem to be overcome. The size of even "small" peptides Is larger than most common drug molecules, and it is usually desirable, if for no other reason than ease of synthesis, to simplify the structures as much as possible. Finally, for the small number of peptides which have been studied by the oral route, poor bloavallablllty has been a problem. 

Sakuma, S., Hayashi, M., and Akashi, M. Design of nanoparticles composed of graft copolymers for oral peptide delivery. Adv. Drug Del. Rev. 47 21—37, 2001. 

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. 

Pauletti, G.M., S. Gangwar,T.J. Siahaan, A. Jeffrey, and R.T. Borchardt. 1997. Improvement of oral peptide bioavailability Peptidomimetics and prodrug strategies. Adv. Drug Deliv. Rev. 27 235-256. 

Werle, M. (2006) Innovations in oral peptide delivery. Future Drug Deliver. 39 10. 

Luessen HL, Verhoef JC, Borchard G, Lehr CM, de Boer AG, Junginger HE (1995) Mucoadhesive polymers in peroral peptide drug delivery. II. Carbomer and polycarbophil are potent inhibitors of the intestinal proteolytic enzyme trypsin. Pharm Res 12 1293-1298 Marschutz MK, Bernkop-Schnurch A (2000) Oral peptide drug delivery polymer-inhibitor conjugates protecting insulin from enzymatic degradation in vitro. Biomaterials 21 1499-1507... 

Van der Merwe, Verhoef, J.C., Kotze, A.F. and Junginger, H.E. (2004b) A-Trimethyl chitosan chloride as absorption enhancer in oral peptide drug delivery. Development and characterization of minitablet and granule formulations. Eur. J. Pharm. Biopharm. 57 85-91. 

Fig. 8.6 Depiction of gastrointestinal barriers to oral peptide drug delivery and strategies to overcome them by the use of multifunctional matrices. Adapted from Bernkop-Schnurch and Walker (2001)...

Bernkop-Schniirch, A. and Walker, G. Multifunctional matrices for oral peptide delivery. Crit. Rev. Ther. Drug Carrier Syst. 2001 18, 5, 459-501. 

As discussed in Chapter 1 (Section 1.1) certain drugs (including peptides, proteins and nucleic acid therapeutics) are unsuitable for oral delivery and must be given intravenously. Research has recently been directed towards the development of alternatives to the parenteral route, such as the transdermal, nasal and other routes thus far discussed in this book, for the systemic delivery of such drugs. 

Kourounakis Rekka ADVANCED DRUG DESIGN AND DEVELOPMENT Labaune HANDBOOK OF PHARMACOKINETICS The Toxicity Asssessment of Chemicals Macheras, Reppas Dressman BIOPHARMACEUTICS OF ORALLY ADMINISTERED DRUGS Martinez PEPTIDE HORMONES AS PROHORMONES Rainsford ANTI-RHEUMATIC DRUGS Actions and Side Effects... 

It is well known that the oral delivery of many drugs, particularly peptides and proteins, is limited due to... 

Figure 9 HPMA copol5nner conjugates designed (i) to deliver drug extracellularly when cleaved by an external trigger (e.g., azo linkers), (ii) to transfer drugs across a biological barrier (e,g., oral peptide vaccine delivery), (iii) for lysosomotropic delivery of anticancer conjugates, or (iv) to deliver macromolecular drugs into the c5d osol via the endosomotropic route.

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