Oral peptide and protein delivery: Intestinal obstacles and commercial prospects

Expert Opinion on Drug Delivery

Volumn 11, Issue 8, 2014, Pages 1323-1335

  Smart, Alice L ^a   Gaisford, Simon ^a   Basit, Abdul W ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

Biopharmaceuticals; Colonic drug targeting; Gastrointestinal metabolism; Insulin; Macromolecules; Oral delivery strategies; Oral peptide protein bioavailability

Indexed keywords

PEPTIDES AND PROTEINS;

DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DELIVERY SYSTEM; DRUG INDUSTRY; GASTROINTESTINAL TRACT; HUMAN; INTESTINE CELL; INTESTINE MUCOSA PERMEABILITY; LARGE INTESTINE; OUTCOME ASSESSMENT; PERMEABILITY BARRIER; PROTEIN DEGRADATION; PROTEIN STABILITY; REVIEW; SMALL INTESTINE; STOMACH; THERAPY EFFECT;

BIOPHARMACEUTICALS; COLONIC DRUG TARGETING; GASTROINTESTINAL METABOLISM; INSULIN; MACROMOLECULES; ORAL DELIVERY STRATEGIES; ORAL PEPTIDE/PROTEIN BIOAVAILABILITY;

ADMINISTRATION, ORAL; BIOLOGICAL AVAILABILITY; CHEMISTRY, PHARMACEUTICAL; DRUG DELIVERY SYSTEMS; HUMANS; INTESTINAL ABSORPTION; PEPTIDES; PROTEINS;

EID: 84904636678     PISSN: 17425247     EISSN: 17447593     Source Type: Journal    
DOI: 10.1517/17425247.2014.917077     Document Type: Review

References (100)

1. IMAP. Pharmaceuticals and Biotech Industry Global Report 2011. Available from: Www.imap.com [Cited 29 April 2014]
2. Top 20 Best-Selling Drugs of 2012. 2013. Available from: Www.genengnews. com [Cited 8 February 2014]
3. Pichereau C, Allary C. Therapeutic peptides under the spotlight. 2005. Available from: Www.bionest.com [Cited 29 April 2014]
4. Reichert J, Pechen P, Tartar A, Dunn MK. Development trends for peptide therapeutics-A comprehensive quantitative analysis of peptide therapeutics in clinical development. Peptide Therapeutics Foundation 2010. 1-11. Available from: Www.peptidetherapeutics.org [Cited 29 April 2014]
5. McConnell EL, Fadda HM, Basit AW. Gut instincts: Explorations in intestinal physiology and drug delivery. Int J Pharm 2008;364(2):213-26
6. Busby RW, Kessler MM, Bartolini WP, et al. Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. J Pharmacol Exp Ther 2013;344(1):196-206
7. Choc MG. Bioavailability and pharmacokinetics of cyclosporine formulations: Neoral vs Sandimmune. Int J Dermatol 1997;36(Suppl 1):1-6
8. Ito Y, Yoshimura M, Tanaka T, et al. Effect of lipophilicity on the bioavailability of drugs after percutaneous administration by dissolving microneedles. J Pharm Sci 2011;101(3):1145-56
9. Cui X, Cao D, Qu C, et al. A study of the chemical and biological stability of vasoactive intestinal peptide. Drug Dev Ind Pharm 2013;39(12):1907-10
10. Fjellestad-Paulsen A, Soderberg-Ahlm C, Lundin S. Metabolism of vasopressin, oxytocin, and their analogues in the human gastrointestinal tract. Peptides 1995;16(6):1141-7
11. Wen JY, Ledger R, McLeod BJ, et al. Protein and peptide degradation in the intestine of the common brushtail possum (Trichosurus vulpecula). J Comp Physiol B 2002;172(7):553-9
12. Tozaki H, Odoriba T, Iseki T, et al. Use of protease inhibitors to improve calcitonin absorption from the small and large intestine in rats. J Pharm Pharmacol 1998;50(8):913-20
13. Wen JY, Ledger R, Butt AG, et al. Inhibition of proteolysis in luminal extracts from the intestine of the brushtail possum. J Pharm Pharmacol 2002;54(10):1365-72
14. Wen JY, Ledger R, McLeod BJ, et al. Enzymatic degradation of luteinizing hormone releasing hormone (LHRH) by mucosal homogenates from the intestine of the common brushtail possum (Trichosurus vulpecula). Life Sci 2002;71(25):3019-30
15. Haupt S, Gil E, Tirosh R, et al. Regional peptide uptake study in the rat intestinal mucosa: Glatiramer acetate as a model drug. Pharm Res 2002;19(6):832-7
16. Ungell AL, Andreasson A, Lundin K, et al. Effects of enzymatic inhibition and increased paracellular shunting on transport of vasopressin analogs in the rat. J Pharm Sci 1992;81(7):640-5
17. Russell-Jones GJ, Westwood SW, Habberfield AD. Vitamin B12 mediated oral delivery systems for granulocytecolony stimulating factor and erythropoietin. Bioconjug Chem 1995;6(4):459-65
18. Torres-Lugo M, Garcia M, Record R, et al. pH-Sensitive hydrogels as gastrointestinal tract absorption enhancers: Transport mechanisms of salmon calcitonin and other model molecules using the Caco-2 cell model. Biotechnol Prog 2002;18(3):612-16
19. Yoo HS, Park TG. Biodegradable nanoparticles containing protein-fatty acid complexes for oral delivery of salmon calcitonin. J Pharm Sci 2004;93(2):488-95
20. Foger F, Kopf A, Loretz B, et al. Correlation of in vitro and in vivo models for the oral absorption of peptide drugs. Amino Acids 2008;35(1):233-41
21. Humphrey MJ, Ringrose PS. Peptides and related drugs: A review of their absorption, metabolism, and excretion. Drug Metab Rev 1986;17(3-4):283-310
22. McMartin C, Hutchinson LE, Hyde R, et al. Analysis of structural requirements for the absorption of drugs and macromolecules from the nasal cavity. J Pharm Sci 1987;76(7):535-40
23. Donovan MD, Flynn GL, Amidon GL. Absorption of polyethylene glycols 600 through 2000: The molecular weight dependence of gastrointestinal and nasal absorption. Pharm Res 1990;Aug;7(8):863-8
24. Jung T, Kamm W, Breitenbach A, et al. Biodegradable nanoparticles for oral delivery of peptides: Is there a role for polymers to affect mucosal uptake?. Eur J Pharm Biopharm 2000;50(1):147-60
25. Conradi RA, Hilgers AR, Ho NF, et al. The influence of peptide structure on transport across Caco-2 cells. Pharm Res 1991;8(12):1453-60
26. 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(12):1710-14
27. Ritschel WA. Microemulsions for improved peptide absorption from the gastrointestinal tract. Methods Find Exp Clin Pharmacol 1991;13(3):205-20
28. Hee Lee Y, Leesman GD, Makhey V, et al. Regional oral absorption, hepatic first-pass effect, and non-linear disposition of salmon calcitonin in beagle dogs. Eur J Pharm Biopharm 2000;50(2):205-11
29. Sinko PJ, Lee YH, Makhey V, et al. Biopharmaceutical approaches for developing and assessing oral peptide delivery strategies and systems: In vitro permeability and in vivo oral absorption of salmon calcitonin (sCT). Pharm Res 1999;16(4):527-33
30. Sasaki I, Fujita T, Murakami M, et al. Intestinal absorption of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue. I. Possible factors for the low oral bioavailability in rats. Biol Pharm Bull 1994;17(9):1256-61
31. d'Agay-Abensour L, Fjellestad-Paulsen A, Hoglund P, et al. Absolute bioavailability of an aqueous solution of 1-deamino-8-D-Arginine vasopressin from different regions of the gastrointestinal tract in man. Eur J Clin Pharmacol 1993;44(5):473-6
32. Han L, Zhao Y, Yin L, et al. Insulin-loaded pH-sensitive hyaluronic acid nanoparticles enhance transcellular delivery. AAPS PharmSciTech 2012;13(3):836-45
33. Lundin S, Pantzar N, Broeders A, et al. Differences in transport rate of oxytocin and vasopressin analogues across proximal and distal isolated segments of the small intestine of the rat. Pharm Res 1991;8(10):1274-80
34. Pantzar N, Lundin S, Westrom BR. Different properties of the paracellular pathway account for the regional small intestinal permeability to the peptide desmopressin. J Pharm Sci 1995;84(10):1245-8
35. Zheng Y, Qiu Y, Lu MF, et al. Permeability and absorption of leuprolide from various intestinal regions in rabbits and rats. Int J Pharm 1999;185(1):83-92
36. Kohler E, Duberow-Drewe M, Drewe J, et al. Absorption of an aqueous solution of a new synthetic somatostatin analogue administered to man by gavage. Eur J Clin Pharmacol 1987;33(2):167-71
37. Gebert A, Steinmetz I, Fassbender S, et al. Antigen transport into Peyer's patches: Increased uptake by constant numbers of M cells. Am J Pathol 2004;164(1):65-72
38. Gupta S, Jain A, Chakraborty M, et al. Oral delivery of therapeutic proteins and peptides: A review on recent developments. Drug Deliv 2013;20(6):237-46
39. McConnell EL, Liu F, Basit AW. Colonic treatments and targets: Issues and opportunities. J Drug Target 2009;17(5):335-63
40. Singh R, Singh S, Lillard JW Jr. Past, present, and future technologies for oral delivery of therapeutic proteins. J Pharm Sci 2008;97(7):2497-523
41. Varum FJ, Hatton GB, Basit AW. Food, physiology and drug delivery. Int J Pharm 2013;457(2):446-60
42. Leone-Bay A, Sato M, Paton D, et al. Oral delivery of biologically active parathyroid hormone. Pharm Res 2001;18(7):964-70
43. Milstein SJ, Leipold H, Sarubbi D, et al. Partially unfolded proteins efficiently penetrate cell membranes-implications for oral drug delivery. J Control Release 1998;53(1-3):259-67
44. Leone-Bay A, McInnes C, Wang N, et al. Microsphere formation in a series of derivatized alpha-Amino acids: Properties, molecular modeling, and oral delivery of salmon calcitonin. J Med Chem 1995;38(21):4257-62
45. Binkley N, Bolognese M, Sidorowicz-Bialynicka A, et al. A phase 3 trial of the efficacy and safety of oral recombinant calcitonin: The Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) trial. J Bone Miner Res 2012;27(8):1821-9
46. Yang R, Gao R, Li F, et al. The influence of lipid characteristics on the formation, in vitro release, and in vivo absorption of protein-loaded SLN prepared by the double emulsion process. Drug Dev Ind Pharm 2011;37(2):139-48
47. Sasaki I, Tamura T, Shibakawa T, et al. Metabolism of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue, by intestinal microorganisms. Pharm Res 1997;14(8):1004-7
48. Anderson KE, Eliot LA, Stevenson BR, et al. Formulation and evaluation of a folic acid receptor-Targeted oral vancomycin liposomal dosage form. Pharm Res 2001;18(3):316-22
49. Fricker G, Bruns C, Munzer J, et al. Intestinal absorption of the octapeptide SMS 201-995 visualized by fluorescence derivatization. Gastroenterology 1991;100(6):1544-52
50. Michael S, Thole M, Dillmann R, et al. Improvement of intestinal peptide absorption by a synthetic bile acid derivative, cholylsarcosine. Eur J Pharm Sci 2000;10(2):133-40
51. Thanou M, Verhoef JC, Marbach P, et al. Intestinal absorption of octreotide: N-Trimethyl chitosan chloride (TMC) ameliorates the permeability and absorption properties of the somatostatin analogue in vitro and in vivo. J Pharm Sci 2000;89(7):951-7
52. Adjei A, Love S, Johnson E, et al. Effect of formulation adjuvants on gastrointestinal absorption of leuprolide acetate. J Drug Target 1993;1(3):251-8
53. Iqbal J, Vigl C, Moser G, et al. Development and in vivo evaluation of a new oral nanoparticulate dosage form for leuprolide based on polyacrylic acid. Drug Deliv 2011;18(6):432-40
54. Iqbal J, Shahnaz G, Perera G, et al. Thiolated chitosan: Development and in vivo evaluation of an oral delivery system for leuprolide. Eur J Pharm Biopharm 2012;80(1):95-102
55. Luessen HL, de Leeuw BJ, Langemeyer MW, et al. Mucoadhesive polymers in peroral peptide drug delivery. VI. Carbomer and chitosan improve the intestinal absorption of the peptide drug buserelin in vivo. Pharm Res 1996;13(11):1668-72
56. Thanou M, Florea BI, Langemeyer MW, et al. N-Trimethylated chitosan chloride (TMC) improves the intestinal permeation of the peptide drug buserelin in vitro (Caco-2 cells) and in vivo (rats). Pharm Res 2000;17(1):27-31
57. Lundin S, Folkesson HG, Pierzynovski SG, et al. Gastrointestinal absorption and plasma clearance rates of [D-Arg8]vasopressin analogues in the rat. Peptides 1994;15(5):809-14
58. Fjellestad-Paulsen A, d'Agay-Abensour L, Hoglund P, et al. Bioavailability of 1-deamino-8-D-Arginine vasopressin with an enzyme inhibitor (aprotinin) from the small intestine in healthy volunteers. Eur J Clin Pharmacol 1996;50(6):491-5
59. Jaiswal J, Gupta SK, Kreuter J. Preparation of biodegradable cyclosporine nanoparticles by high-pressure emulsification-solvent evaporation process. J Control Release 2004;96(1):169-78
60. Ogiso T, Funahashi N, Tsukioka Y, et al. Oral delivery of synthetic eel calcitonin, elcatonin, in rats. Biol Pharm Bull 2001;24(6):656-61
61. Tozaki H, Nishioka J, Komoike J, et al. Enhanced absorption of insulin and (Asu (1,7))eel-calcitonin using novel azopolymer-coated pellets for colonspecific drug delivery. J Pharm Sci 2001;90(1):89-97
62. Fetih G, Fausia H, Okada N, et al. Colon-specific delivery and enhanced colonic absorption of [Asu(1,7)]-eel calcitonin using chitosan capsules containing various additives in rats. J Drug Target 2006;14(3):165-72
63. Sinko PJ, Smith CL, McWhorter LT, et al. Utility of pharmacodynamic measures for assessing the oral bioavailability of peptides. 1. Administration of recombinant salmon calcitonin in rats. J Pharm Sci 1995;84(11):1374-8
64. du Plessis LH, Lubbe J, Strauss T, et al. Enhancement of nasal and intestinal calcitonin delivery by the novel Pheroid fatty acid based delivery system, and by N-Trimethyl chitosan chloride. Int J Pharm 2010;385(1-2):181-6
65. Hastewell J, Lynch S, Williamson I, et al. Absorption of human calcitonin across the rat colon in vivo. Clin Sci (Lond) 1992;82(5):589-94
66. Buclin T, Cosma Rochat M, Burckhardt P, et al. Bioavailability and biological efficacy of a new oral formulation of salmon calcitonin in healthy volunteers. J Bone Miner Res 2002;17(8):1478-85
67. Hastewell J, Antonin KH, Fox R, et al. The colonic absorption of human calcitonin: The effects of increasing local concentration and co-Administration with a protease inhibitor. Int J Pharm 1995;126(1-2):245-51
68. Jin CH, Chae SY, Son S, et al. A new orally available glucagon-like peptide-1 receptor agonist, biotinylated exendin-4, displays improved hypoglycemic effects in db/db mice. J Control Release 2009;133(3):172-7
69. Gedulin BR, Smith PA, Jodka CM, et al. Pharmacokinetics and pharmacodynamics of exenatide following alternate routes of administration. Int J Pharm 2008;356(1-2):231-8
70. Takeuchi H, Yamamoto H, Niwa T, et al. Enteral absorption of insulin in rats from mucoadhesive chitosan-coated liposomes. Pharm Res 1996;13(6):896-901
71. Yamamoto A, Tanaka H, Okumura S, et al. Evaluation of insulin permeability and effects of absorption enhancers on its permeability by an in vitro pulmonary epithelial system using Xenopus pulmonary membrane. Biol Pharm Bull 2001;24(4):385-9
72. Eaimtrakarn S, Rama Prasad YV, Ohno T, et al. Absorption enhancing effect of labrasol on the intestinal absorption of insulin in rats. J Drug Target 2002;10(3):255-60
73. Guo L, Ma E, Zhao H, et al. Preliminary evaluation of a novel oral delivery system for rhPTH1-34: In vitro and in vivo. Int J Pharm 2011;420(1):172-9
74. Venkatesan N, Uchino K, Amagase K, et al. Gastro-intestinal patch system for the delivery of erythropoietin. J Control Release 2006;Mar;10;111(1-2):19-26
75. Bayley D, Temple C, Clay V, et al. The transmucosal absorption of recombinant human interferon-Alpha B/D hybrid in the rat and rabbit. J Pharm Pharmacol 1995;47(9):721-4
76. Jensen-Pippo KE, Whitcomb KL, DePrince RB, et al. Enteral bioavailability of human granulocyte colony stimulating factor conjugated with poly(ethylene glycol). Pharm Res 1996;13(1):102-7
77. Moore JA, Pletcher SA, Ross M. Absorption enhancement of growth hormone from the gastrointestinal tract of rats. Int J Pharm 1986;34:35-43
78. Khomane K, Kumar L, Meena CL, et al. NP-647, a novel TRH analogue: Investigating physicochemical parameters critical for its oral and parenteral delivery. Int J Pharm 2011;406(1-2):21-30
79. Kafka AP, McLeod BJ, Rades T, et al. Release and bioactivity of PACA nanoparticles containing D-Lys-GnRH for brushtail possum fertility control. J Control Release 2011;149(3):307-13
80. Werle M, Samhaber A, Bernkop-Schnurch A. Degradation of teriparatide by gastro-intestinal proteolytic enzymes. J Drug Target 2006;14(3):109-15
81. Jain S, Rathi VV, Jain AK, et al. Folate-decorated PLGA nanoparticles as a rationally designed vehicle for the oral delivery of insulin. Nanomedicine (Lond) 2012;May;14;7(9):1311-37
82. Werle M, Kolmar H, Albrecht R, et al. Characterisation of the barrier caused by luminally secreted gastro-intestinal proteolytic enzymes for two novel cystine-knot microproteins. Amino Acids 2008;35(1):195-200
83. Zheng C, Liu Y, Zhou Q, et al. Capillary electrophoresis with noncovalently bilayer-coated capillaries for stability study of allergenic proteins in simulated gastrointestinal fluids. J Chromatogr B Analyt Technol Biomed Life Sci 2010;878(28):2933-6
84. Massicotte LP, Baille WE, Mateescu MA. Carboxylated high amylose starch as pharmaceutical excipients. Structural insights and formulation of pancreatic enzymes. Int J Pharm 2008;356(1-2):212-23
85. Scocca S, Faustini M, Villani S, et al. Alginate/polymethacrylate copolymer microparticles for the intestinal delivery of enzymes. Curr Drug Deliv 2007;4(2):103-8
86. Li XY, Jin LJ, Uzonna JE, et al. Chitosan-Alginate microcapsules for oral delivery of egg yolk immunoglobulin (IgY): In vivo evaluation in a pig model of enteric colibacillosis. Vet Immunol Immunopathol 2009;129(1-2):132-6
87. Thwaites DT, Simmons NL, Hirst BH. Thyrotropin-releasing hormone (TRH) uptake in intestinal brush-border membrane vesicles: Comparison with proton-coupled dipeptide and Na(+)-coupled glucose transport. Pharm Res 1993;10(5):667-73
88. Fagerholm U, Sjostrom B, Sroka-Markovic J, et al. The effect of a drug-delivery system consisting of soybean phosphatidyl choline and medium-chain monoacylglycerol on the intestinal permeability of hexarelin in the rat. J Pharm Pharmacol 1998;50(5):467-73
89. Lundin S, Bengtsson HI, Folkesson HG, et al. Degradation of [mercaptopropionic acid1, D-Arginine8]-vasopressin (dDAVP) in pancreatic juice and intestinal mucosa homogenate. Pharmacol Toxicol 1989;65(2):92-5
90. Guo J, Ping Q, Jiang G, et al. Transport of leuprolide across rat intestine, rabbit intestine and Caco-2 cell monolayer. Int J Pharm 2004;278(2):415-22
91. Zheng Y, FuLu MY, Qiu Y, et al. Enzymatic degradation of leuprolide in rat intestinal mucosal homogenates. Pharm Dev Technol 1999;4(4):539-44
92. Lee HE, Lee MJ, Park CR, et al. Preparation and characterization of salmon calcitonin-sodium triphosphate ionic complex for oral delivery. J Control Release 2010;143(2):251-7
93. Lu RH, Kopeckova P, Kopecek J. Degradation and aggregation of human calcitonin in vitro. Pharm Res 1999;16(3):359-67
94. Youn YS, Jung JY, Oh SH, et al. Improved intestinal delivery of salmon calcitonin by Lys18-Amine specific PEGylation: Stability, permeability, pharmacokinetic behavior and in vivo hypocalcemic efficacy. J Control Release 2006;114(3):334-42
95. Youn YS, Chae SY, Lee S, et al. Improved peroral delivery of glucagonlike peptide-1 by site-specific biotin modification: Design, preparation, and biological evaluation. Eur J Pharm Biopharm 2008;68(3):667-75
96. Chae SY, Jin CH, Shin HJ, et al. Preparation, characterization, and application of biotinylated and biotin-PEGylated glucagon-like peptide-1 analogues for enhanced oral delivery. Bioconjug Chem 2008;19(1):334-41
97. Tozaki H, Emi Y, Horisaka E, et al. Degradation of insulin and calcitonin and their protection by various protease inhibitors in rat caecal contents: Implications in peptide delivery to the colon. J Pharm Pharmacol 1997;49(2):164-8
98. Tozaki H, Emi Y, Horisaka E, et al. Metabolism of peptide drugs by the microorganisms in rat cecal contents. Biol Pharm Bull 1995;18(6):929-31
99. Soltero R, Ekwuribe N. The oral delivery of protein and peptide drug-A report. Innovat Pharmaceut Technol 2001;1:106-110
100. Eldor R, Kidron M, Greenberg-Shushlav Y, et al. Novel glucagon-like peptide-1 analog delivered orally reduces postprandial glucose excursions in porcine and canine models. J Diabetes Sci Technol 2010;4(6):1516-23.