PEPTIDES: A NEW THERAPEUTIC APPROACH
Peptide therapeutics have played a notable role in medical practice since the advent of insulin therapy in the 1920s. Over 60 peptide drugs are approved in the United States and other major markets, and peptides continue to enter clinical development at a steady pace. Peptide drug discovery has diversified beyond its traditional focus on endogenous human peptides to include a broader range of structures identified from other natural sources or through medicinal chemistry efforts. Peptides are recognized for being highly selective and efficacious and, at the same time, relatively safe and well tolerated. Consequently, there is an increased interest in peptides in pharmaceutical research and development (R and D), and approximately 140 peptide therapeutics are currently being evaluated in clinical trials. Given that the low-hanging fruits in the form of obvious peptide targets have already been picked, it has now become necessary to explore new routes beyond traditional peptide design. Examples of such approaches are multifunctional and cell-penetrating peptides, as well as peptide drug conjugates. In regards to patient compliance for drug delivery, oral drug delivery is generally the preferred route of administration. However, parental injection of peptide drugs has always been the primary method of peptide drug administration. Nevertheless, oral delivery of peptide drug presents a significant challenge due to the enzymatic degradation by enzymes in the GI tract and the poor penetration of the peptides across gastro-intestinal epithelium membranes, particularly for adults. Therefore, a novel peptide drug analogue or pro-drug that both protect peptide drugs from degradation by the enzymes in the GI tract that also improves its penetration across the intestinal epithelium membrane would greatly advance the development of peptide drugs as effective candidates for the treatment of various diseases.
2. Elkinton JR, Hunt Jr AD. Effects of pituitary adrenocorticotropic hormone (ACTH) therapy. J Am Med Assoc 1949;141:1273â€“9.
3. Adessi C, Soto C. Converting a peptide into a drug: strategies to improve stability and bioavailability. Curr Med Chem 2002;9:963-78.
4. Aungst B, Saitoh H, Burcham D, Huand S, Mousa S, Hussain M. Enhancement of the intestinal absorption of peptides and nonpeptides. J Controlled Release 1996;41:19â€“31.
5. Hollenstein K, de Graaf C, Bortolato A, Wang MW, Marshall FH, Stevens RC. Insights into the structure of class B GPCRs. Trends Pharmacol Sci 2014;35:12â€“22.
6. Agoulnik AI, Agoulnik IU, Hu X, Marugan J. Synthetic non-peptide low molecular weight agonists of the relaxin receptor 1. Br J Pharmacol 2017;174:977â€“89.
7. Hamman JH, Enslin GM, Kotze AF. Oral delivery of peptide drugs: barriers and developments. Bio Drugs 2005;19:165â€“77.
8. T Borchardt R, Jeffrey Aube, Siahaan TJ, Gangwar S, Pauletti GM. Improvement of oral peptide bioavailability: peptide-mimetics and prodrug strategies. Adv Drug Delivery Rev 1997;27:235-56.
9. Kim DC, Burton PS, Borchardt RT. A correlation between the permeability characteristics of a series of peptides using an in vitro cell-culture model (caco-2) and those using an in-situ perfused rat ileum model of the intestinal mucosa. Pharm Res 1993;10:1710-4.
10. Lalatsa A, Lee V, Malkinson JP, Zloh M, SchAtzlein AG. A prodrug nanoparticle approach for the oral delivery of a hydrophilic peptide, leucine-enkephalin, to the brain. Mol Pharm 2012;9:1665-80.
11. Veronese FM, Harris JM. Introduction and overview of peptide and protein pegylation. Adv Drug Delivery Rev 2002;54:453â€“6.
12. Mahato RI, Narang AS, Thoma L, Miller DD. Emerging trends in oral delivery of peptide and protein drugs. Crit Rev Ther Drug Carr Syst 2003;20:153-214.
13. Bernkop-Schnurch A. Chitosan and its derivatives: potential excipients for peroral peptide delivery systems. Int J Pharm 2000;194:1-13.
14. Bernkop-Schnurch A, Krajicek ME. Mucoadhesive polymers as platforms for peroral peptide delivery and absorption: synthesis and evaluation of different chitosan-edta conjugates. J Controlled Release 1998;50:215-23.
15. Talegaonkar S, Azeem A, Ahmad FJ, Khar RK, Pathan SA. Microemulsions: a novel approach to enhanced drug delivery. Recent Pat Drug Delivery Formul 2008;2:238-57.
16. Jung T, Kamm W, Breitenbach A, Kaiserling E, Xiao JX, Kissel T. Biodegradable nanoparticles for oral delivery of peptides: is there a role for polymers to affect mucosal uptake? Eur J Pharm Biopharm 2000;50:147â€“60.
17. Yah CS, Simate GS, Iyuke SE. Nanoparticles toxicity and their routes of exposures. Pak J Pharm Sci 2012;25:477â€“91.
18. Iwanaga K, Ono S, Narioka K. Application of surface-coated liposomes for oral delivery of peptide: effects of coating the liposome's surface on the GI transit of insulin. J Pharm Sci 1999;88:248â€“52.
19. Vyas SP, Venugopalan P, Sood A, Mysore N. Some approaches to improve the bioavailability of peptides and proteins through oral and other mucosal routes. Pharmazie 1997;52:339-45.
20. Thomas DW, Burns J, Audette J, Carroll A, Dow-Hygelund C, Hay M. Clinical development success rates; 2006â€“2015. 2016.
21. Hattori M, Taylor TD. The human intestinal microbiome: a new frontier of human biology. DNA Res 2009;16:1â€“12.
22. Pocai A. Glucagon-like peptide 1/glucagon receptor dual agonism reverses obesity in mice. Diabetes 2009;58:2258â€“66.
23. Fosgerau K. The new glucagon-GLP-1 dual agonist ZP2929 in combination with long-acting insulin improves glycemic control without causing weight loss in db/db mice. Diabetes 2011;60:A408â€“A442.
24. Fosgerau K. The novel GLP-1-gastrin dual agonist, ZP3022, increases beta-cell mass and prevents diabetes in db/db mice. Diabetes Obes Metab 2013;15:62â€“71.
25. Zhou L, Bohn LM. Functional selectivity of GPCR signalling in animals. Curr Opin Cell Biol 2014;27:102â€“8.
26. Abbara A, Jayasena CN, Christopoulos G. Efficacy of kisspeptin-54 to trigger oocyte maturation in women at high risk of ovarian hyperstimulation syndrome (OHSS) during in vitro fertilization (IVF) therapy. J Clin Endocrinol Metab 2015;100:3322â€“31.
27. FDA Guidance for industry. ANDAs for certain highly purified synthetic peptide products that refer to listed drugs of recombinant DNA origin; 2017.
28. Dhanda SK, Usmani SS, Agrawal P, Nagpal G, Gautam A, Raghava GP. Novel in silico tools for designing peptide-based subunit vaccines and immunotherapeutic. Brief Bioinform 2017;18:467-78.
29. Leader B, Baca QJ, Golan DE. Protein therapeutics: a summary and pharmacological classification. Nat Rev Drug Discovery 2008;7:21-39.
30. Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, et al. ChEMBL: a large-scale bioactivity database for drug discovery. Nucleic Acids Res 2012;40:D1100-7.
31. Walther A, Riehemann K, Gerke V. A novel ligand of the formyl peptide receptor: annexin I regulates neutrophil extravasation by interacting with the FPR. Mol Cell 2000;5:831â€“40.