Peroral delivery of peptide drugs

American Pharmaceutical Review

Volumn 11, Issue 3, 2008, Pages

  Cheng, Weiqiang ^a   Lim, Lee Yong ^b  

^a UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^b UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOPEPTIDASE; BILE SALT; BRAIN NATRIURETIC PEPTIDE; CALCITONIN; CARBOPOL 934; CARBOXYMETHYLCELLULOSE; CARBOXYPEPTIDASE; CHITOSAN; CHYMOTRYPSIN; CYCLOSPORIN; DODECYL SULFATE SODIUM; ELASTASE; ETHYL CELLULOSE; HEXYL INSULIN MONOCONJUGATE 2; INSULIN; MACROGOL; MEMBRANE PHOSPHOLIPID; OCTREOTIDE; PECTIN; PEPTIDE; POLYGLACTIN; POLYOXYETHYLENE DERIVATIVE; POLYSORBATE 80; SALCATONIN; TAUROCHOLIC ACID; TAURODEOXYCHOLIC ACID; TRANSFERRIN; TRYPSIN;

CELL STRAIN CACO 2; CLINICAL TRIAL; DOG; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG CONFORMATION; DRUG DEGRADATION; DRUG DELIVERY SYSTEM; DRUG FORMULATION; DRUG HALF LIFE; DRUG PENETRATION; DRUG STABILITY; DRUG TRANSPORT; ENZYME DEGRADATION; ENZYME INHIBITION; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; INTESTINE MUCOSA PERMEABILITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; REVIEW;

EID: 55849114873     PISSN: 10998012     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (94)

1. L. Amidon, and S. Yamashita. The challenge of proteolytic enzymes in intestinal peptide delivery. Journal of Controlled Release 46: 39-57 (1997).
2. Y. Aoki, M. Morishita, K. Asai, B. Akikusa, S. Hosoda, and K. Takayama. Region-dependent role of the mucous/glycocalyx layers in insulin permeation across rat small intestinal membrane. Pharm Res 22: 1854-62 (2005).
3. A. M. Ugolev, L. F. Smirnova, N. N. Iezuitova, N. M. Timofeeva, N. M. Mityushova, V. V. Egorova, and E. M. Parshkov. Distribution of some adsorbed and intrinsic enzymes between the mucosal cells of the rat small intestine and the apical glycocalyx separated from them. FEBS Letters 104: 35-38 (1979).
4. J. Heizmann, P. Langguth, A. Biber, R. Oschmann, H. P. Merkle, and S. Wolffram. Enzymatic cleavage of thymopoietin oligopeptides by pancreatic and intestinal brush-border enzymes. Peptides 17: 1083-9 (1996).
5. J. P. Bai. Subcellular distribution of proteolytic activities degrading bioactive peptides and analogues in the rat small intestinal and colonic enterocytes. J Pharm Pharmacol 46: 671-5 (1994).
6. N. Kobayashi, N. Yamamura, M. Kamagata, A. Kurihara, and T. Ikeda. In vitro metabolism of human and salmon calcitonins in rat liver and kidney evaluated by liquid chromatography-tandem mass spectrometry. Xenobiotica 30: 655-64 (2000).
7. J. R. Pappenheimer. Role of pre-epithelial "unstirred" layers in absorption of nutrients from the human jejunum. J Membr Biol 179: 185-204 (2001).
8. A. W. Larhed, P. Artursson, and E. Bjork. The influence of intestinal mucus components on the diffusion of drugs. Pharm Res 15: 66-71 (1998).
9. J. Filmus, W. Shi, Z. M. Wong, and M. J. Wong. Identification of a new membrane-bound heparan sulphate proteoglycan. Biochem J 311 ( Pt 2): 561-5 (1995).
10. M. Goldberg and I. Gomez-Orellana. Challenges for the oral delivery of macromolecules. Nat Rev Drug Discov 2: 289-95 (2003).
11. M. D. Donovan, G. L. Flynn, and G. L. Amidon. Absorption of polyethylene glycols 600 through 2000: the molecular weight dependence of gastrointestinal and nasal absorption. Pharm Res 7: 863-8 (1990).
12. G. Camenisch, J. Alsenz, H. van de Waterbeemd, and G. Folkers. Estimation of permeability by passive diffusion through Caco-2 cell monolayers using the drugs' lipophilicity and molecular weight. Eur J Pharm Sci 6: 317-24 (1998).
13. H. Gao, F. Wang, and E. J. Lien. Hydrophobic contribution constants of amino acid residues to the hydrophobicities of oligopeptides. Pharm Res 12: 1279-83 (1995).
14. P. S. Burton, R. A. Conradi, N. F. Ho, A. R. Hilgers, and R. T. Borchardt. How structural features influence the biomembrane permeability of peptides. J Pharm Sci 85: 1336-40 (1996).
15. B. Rihova. Receptor-mediated targeted drug or toxin delivery. Adv Drug Deliv Rev 29: 273-289 (1998).
16. A. Bernkop-Schnurch and M. K. Marschutz. Development and in vitro evaluation of systems to protect peptide drugs from aminopeptidase N. PHARM. RES. 14: 181-185 (1997).
17. Y. Birk. The Bowman-Birk inhibitor. Trypsin- and chymotrypsininhibitor from soybeans. International Journal Of Peptide And Protein Research 25: 113-131 (1985).
18. R. B. Shah and M. A. Khan. Protection of salmon calcitonin breakdown with serine proteases by various ovomucoid species for oral drug delivery. J Pharm Sci 93: 392-406 (2004).
19. C. W. Garner, Jr. and F. J. Behal. Human liver aminopeptidase. Role of metal ions in mechanism of action. Biochemistry 13: 3227-33 (1974).
20. R. B. Shah, A. Palamakula, and M. A. Khan. Cytotoxicity evaluation of enzyme inhibitors and absorption enhancers in Caco-2 cells for oral delivery of salmon calcitonin. J Pharm Sci 93: 1070-82 (2004).
21. Å. Krogdahl, B. Leat, and J. J. OLLI. Soybean proteinase inhibitors affect intestinal trypsin activities and amino acid digestibilities in rainbow trout (Oncorhynchus mykiss). Comp. biochem. physiol., Part A, Physiol. 107: 215-219 (1994).
22. J. E. Reseland, H. Holm, M. B. Jacobsen, T. G. Jenssen, and L. E. Hanssen. Proteinase inhibitors induce selective stimulation of human trypsin and chymotrypsin secretion. J Nutr 126: 634-42 (1996).
23. R. N. Melmed, A. A. A. El-Aaser, and S. J. Holt. Hypertrophy and hyperplasia of the neonatal rat exocrine pancreas induced by orally administered soybean trypsin inhibitor. Biochimica et Biophysica Acta (BBA) - General Subjects 421: 280-288 (1976).
24. Y. C. Ge and R. G. Morgan. The effect of trypsin inhibitor on the pancreas and small intestine of mice. Br J Nutr 70: 333-45 (1993).
25. E. S. Swenson, W. B. Milisen, and W. Curatolo. Intestinal permeability enhancement: efficacy, acute local toxicity, and reversibility. Pharm Res 11: 1132-42 (1994).
26. Y. Watanabe, Y. Matsumoto, N. Hori, H. Funato, and M. Matsumoto. Enhanced rectal absorption of insulin in rabbits from hollow-type suppositories containing insulin and glyceryl-1-monooctanoate. Chem Pharm Bull (Tokyo) 39: 3007-12 (1991).
27. K. Ichikawa, I. Ohata, M. Mitomi, S. Kawamura, H. Maeno, and H. Kawata. Rectal absorption of insulin suppositories in rabbits. J Pharm Pharmacol 32: 314-8 (1980).
28. S. Takatsuka, T. Morita, A. Koguchi, Y. Horikiri, H. Yamahara, and H. Yoshino. Synergistic absorption enhancement of salmon calcitonin and reversible mucosal injury by applying a mucolytic agent and a nonionic surfactant. Int J Pharm (2006).
29. Z. Ma and L. Y. Lim. Uptake of Chitosan and Associated Insulin in Caco-2 Cell Monolayers: A Comparison Between Chitosan Molecules and Chitosan Nanoparticles. Pharm Res. 20: 1812-1819 (2003).
30. J. Smith, E. Wood, and M. Dornish. Effect of Chitosan on Epithelial Cell Tight Junctions. Pharmaceutical Research 21: 43-49 (2004).
31. M. Thanou, J. C. Verhoef, P. Marbach, and H. E. Junginger. 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 89: 951-7 (2000).
32. A. Fasano and S. Uzzau. Modulation of intestinal tight junctions by Zonula occludens toxin permits enteral administration of insulin and other macromolecules in an animal model. J Clin Invest 99: 1158-64 (1997).
33. N. G. Schipper, S. Olsson, J. A. Hoogstraate, A. G. deBoer, K. M. Varum, and P. Artursson. Chitosans as absorption enhancers for poorly absorbable drugs 2: mechanism of absorption enhancement. Pharm Res 14: 923-9 (1997).
34. A. Fasano, C. Fiorentini, G. Donelli, S. Uzzau, J. B. Kaper, K. Margaretten, X. Ding, S. Guandalini, L. Comstock, and S. E. Goldblum. Zonula occludens toxin modulates tight junctions through protein kinase Cdependent actin reorganization, in vitro. J Clin Invest 96: 710-20 (1995).
35. H. E. Hofland, J. A. Bouwstra, J. C. Verhoef, G. Buckton, B. Z. Chowdry, M. Ponec, and H. E. Junginger. Safety aspects of nonionic surfactant vesicles: a toxicity study related to the physicochemical characteristics of non-ionic surfactants. J Pharm Pharmacol 44: 287-94 (1992).
36. E. Scott Swenson and W. J. Curatolo. (C) Means to enhance penetration : (2) Intestinal permeability enhancement for proteins, peptides and other polar drugs: mechanisms and potential toxicity. Advanced Drug Delivery Reviews 8: 39-92 (1992).
37. A. Leone-Bay, K. K. Ho, R. Agarwal, R. A. Baughman, K. Chaudhary, F. DeMorin, L. Genoble, C. McInnes, C. Lercara, S. Milstein, D. O'Toole, D. Sarubbi, B. Variano, and D. R. Paton. 4-[4- [(2-Hydroxybenzoyl)amino] phenyl]butyric acid as a novel oral delivery agent for recombinant human growth hormone. J Med Chem 39: 2571-8 (1996).
38. A. Leone-Bay, M. Sato, D. Paton, A. H. Hunt, D. Sarubbi, M. Carozza, J. Chou, J. McDonough, and R. A. Baughman. Oral delivery of biologically active parathyroid hormone. Pharm Res 18: 964-70 (2001).
39. S. J. Milstein, H. Leipold, D. Sarubbi, A. Leone-Bay, G. M. Mlynek, J. R. Robinson, M. Kasimova, and E. Freire. Partially unfolded proteins efficiently penetrate cell membranes--implications for oral drug delivery. J Control Release 53: 259-67 (1998).
40. T. Buclin, M. Cosma Rochat, P. Burckhardt, M. Azria, and M. Attinger. Bioavailability and biological efficacy of a new oral formulation of salmon calcitonin in healthy volunteers. J Bone Miner Res 17: 1478-85 (2002).
41. M. P. Desai, V. Labhasetwar, G. L. Amidon, and R. J. Levy. Gastrointestinal uptake of biodegradable microparticles: effect of particle size. Pharm Res 13: 1838-45 (1996).
42. S. Sakuma, R. Sudo, N. Suzuki, H. Kikuchi, M. Akashi, Y. Ishida, and M. Hayashi. Behavior of mucoadhesive nanoparticles having hydrophilic polymeric chains in the intestine. J Control Release 81: 281-90 (2002).
43. Z. Ma, T. M. Lim, and L. Y. Lim. Pharmacological activity of peroral chitosan-insulin nanoparticles in diabetic rats. Int J Pharm 293: 271-80 (2005).
44. D. Guggi, A. H. Krauland, and A. Bernkop-Schnurch. Systemic peptide delivery via the stomach: in vivo evaluation of an oral dosage form for salmon calcitonin. J Control Release 92: 125-35 (2003).
45. C. Prego, M. Fabre, D. Torres, and M. J. Alonso. Efficacy and mechanism of action of chitosan nanocapsules for oral Peptide delivery. Pharm Res 23: 549-56 (2006).
46. M. Huang, E. Khor, and L. Y. Lim. Uptake and cytotoxicity of chitosan molecules and nanoparticles: effects of molecular weight and degree of deacetylation. Pharm Res 21: 344-53 (2004).
47. S. Sakuma, Y. Ishida, R. Sudo, N. Suzuki, H. Kikuchi, K.-i. Hiwatari, A. Kishida, M. Akashi, and M. Hayashi. Stabilization of salmon calcitonin by polystyrene nanoparticles having surface hydrophilic polymeric chains, against enzymatic degradation. International Journal of Pharmaceutics 159: 181-189 (1997).
48. A. M. Lowman, M. Morishita, M. Kajita, T. Nagai, and N. A. Peppas. Oral delivery of insulin using pH-responsive complexation gels. J Pharm Sci 88: 933-7 (1999).
49. K. Nakamura, R. J. Murray, J. I. Joseph, N. A. Peppas, M. Morishita, and A. M. Lowman. Oral insulin delivery using P(MAA-g- EG) hydrogels: effects of network morphology on insulin delivery characteristics. J Control Release 95: 589-99 (2004).
50. M. Morishita, T. Goto, K. Nakamura, A. M. Lowman, K. Takayama, and N. A. Peppas. Novel oral insulin delivery systems based on complexation polymer hydrogels: Single and multiple administration studies in type 1 and 2 diabetic rats. J Control Release 110: 587-94 (2006).
51. K. Whitehead, Z. Shen, and S. Mitragotri. Oral delivery of macromolecules using intestinal patches: applications for insulin delivery. J Control Release 98: 37-45 (2004).
52. H. L. Luessen, G. Borchard, A. de Boer, H. Junginger, K. Kolter, V. Schehlmann, and A. Sanner. Use of (meth) acrylic acid/maleic acid copolymers for improving mucosal permeability. In U. S. P. a. T. Office (ed) (U. S. P. a. T. Office, ed), BASF Aktiengesellschaft, 1999.
53. F. A. Dorkoosh, J. C. Verhoef, J. H. Verheijden, M. Rafiee-Tehrani, G. Borchard, and H. E. Junginger. Peroral absorption of octreotide in pigs formulated in delivery systems on the basis of superporous hydrogel polymers. Pharm Res 19: 1532-6 (2002).
54. F. A. Dorkoosh, C. A. Broekhuizen, G. Borchard, M. Rafiee-Tehrani, J. C. Verhoef, and H. E. Junginger. Transport of octreotide and evaluation of mechanism of opening the paracellular tight junctions using superporous hydrogel polymers in Caco-2 cell monolayers. J Pharm Sci 93: 743-52 (2004).
55. F. A. Dorkoosh, J. C. Verhoef, G. Borchard, M. Rafiee-Tehrani, and H. E. Junginger. Development and characterization of a novel peroral peptide drug delivery system. J Control Release 71: 307-18 (2001).
56. F. A. Dorkoosh, M. P. Stokkel, D. Blok, G. Borchard, M. Rafiee- Tehrani, J. C. Verhoef, and H. E. Junginger. Feasibility study on the retention of superporous hydrogel composite polymer in the intestinal tract of man using scintigraphy. J Control Release 99: 199-206 (2004).
57. K. D. Hinds and S. W. Kim. Effects of PEG conjugation on insulin properties. Adv Drug Deliv Rev 54: 505-30 (2002).
58. J. M. Harris and R. B. Chess. Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov 2: 214-21 (2003).
59. J. Ramon, V. Saez, R. Baez, R. Aldana, and E. Hardy. PEGylated interferon-alpha2b: a branched 40K polyethylene glycol derivative. Pharm Res 22: 1374-86 (2005).
60. J. M. Harris, N. E. Martin, and M. Modi. Pegylation: a novel process for modifying pharmacokinetics. Clin Pharmacokinet 40: 539-51 (2001).
61. K. C. Lee, M. O. Park, D. H. Na, Y. S. Youn, S. D. Lee, S. D. Yoo, H. S. Lee, and P. P. DeLuca. Intranasal delivery of PEGylated salmon calcitonins: hypocalcemic effects in rats. Calcif Tissue Int 73: 545-9 (2003).
62. P. Calceti, S. Salmaso, G. Walker, and A. Bernkop-Schnurch. Development and in vivo evaluation of an oral insulin-PEG delivery system. Eur J Pharm Sci 22: 315-23 (2004).
63. H. L. Luessen, J. C. Verhoef, G. Borchard, C. M. Lehr, A. G. de Boer, and H. E. Junginger. Mucoadhesive polymers in peroral peptide drug delivery. II. Carbomer and polycarbophil are potent inhibitors of the intestinal proteolytic enzyme trypsin. Pharm Res 12: 1293-8 (1995).
64. V. M. Leitner, G. F. Walker, and A. Bernkop-Schnurch. Thiolated polymers: evidence for the formation of disulphide bonds with mucus glycoproteins. Eur J Pharm Biopharm 56: 207-14 (2003).
65. D. H. Na, Y. S. Youn, E. J. Park, J. M. Lee, O. R. Cho, K. R. Lee, S. D. Lee, S. D. Yoo, P. P. DeLuca, and K. C. Lee. Stability of PEGylated salmon calcitonin in nasal mucosa. J Pharm Sci 93: 256-61 (2004).
66. C. M. Chin, M. Gutierrez, J. G. Still, and G. Kosutic. Pharmacokinetics of modified oral calcitonin product in healthy volunteers. Pharmacotherapy 24: 994-1001 (2004).
67. A. Cataliotti, J. A. Schirger, F. L. Martin, H. H. Chen, P. M. McKie, G. Boerrigter, L. C. Costello-Boerrigter, G. Harty, D. M. Heublein, S. M. Sandberg, K. D. James, M. A. Miller, N. B. Malkar, K. Polowy, and J. C. Burnett, Jr. Oral human brain natriuretic peptide activates cyclic guanosine 3′,5′- monophosphate and decreases mean arterial pressure. Circulation 112: 836-40 (2005).
68. M. A. Miller, N. B. Malkar, D. Severynse-Stevens, K. G. Yarbrough, M. J. Bednarcik, R. E. Dugdell, M. E. Puskas, R. Krishnan, and K. D. James. Amphiphilic conjugates of human brain natriuretic Peptide designed for oral delivery: in vitro activity screening. Bioconjug Chem 17: 267-74 (2006).
69. C. A. DiCostanzo, M. C. Moore, M. Lautz, M. Scott, B. Farmer, C. A. Everett, J. G. Still, A. Higgins, and A. D. Cherrington. Simulated first-phase insulin release using Humulin or insulin analog HIM2 is associated with prolonged improvement in postprandial glycemia. Am J Physiol Endocrinol Metab 289: E46-52 (2005).
70. S. Clement, P. Dandona, J. G. Still, and G. Kosutic. Oral modified insulin (HIM2) in patients with type 1 diabetes mellitus: results from a phase I/II clinical trial. Metabolism 53: 54-8 (2004).
71. M. Kipnes, P. Dandona, D. Tripathy, J. G. Still, and G. Kosutic. Control of postprandial plasma glucose by an oral insulin product (HIM2) in patients with type 2 diabetes. Diabetes Care 26: 421-6 (2003).
72. S. V. Komarova, J. B. Shum, L. A. Paige, S. M. Sims, and S. J. Dixon. Regulation of osteoclasts by calcitonin and amphiphilic calcitonin conjugates: role of cytosolic calcium. Calcif Tissue Int 73: 265-73 (2003).
73. H. M. Ekrami, A. R. Kennedy, and W. C. Shen. Water-soluble fatty acid derivatives as acylating agents for reversible lipidization of polypeptides. FEBS Lett 371: 283-6 (1995).
74. M. Hashimoto, K. Takada, Y. Kiso, and S. Muranishi. Synthesis of palmitoyl derivatives of insulin and their biological activities. Pharm Res 6: 171-6 (1989).
75. S. Lee, K. Kim, T. S. Kumar, J. Lee, S. K. Kim, D. Y. Lee, Y. K. Lee, and Y. Byun. Synthesis and biological properties of insulindeoxycholic acid chemical conjugates. Bioconjug Chem 16: 615-20 (2005).
76. W. Cheng, S. Satyanarayanajois, and L. Y. Lim. Aqueous-soluble, non-reversible lipid conjugate of salmon calcitonin: synthesis, characterization and in vivo activity. Pharm Res 24: 99-110 (2007).
77. F. Delie, P. Couvreur, D. Nisato, J. B. Michel, F. Puisieux, and Y. Letourneux. Synthesis and in vitro study of a diglyceride prodrug of a peptide. Pharm Res 11: 1082-7 (1994).
78. J. Wang and W. C. Shen. Gastric retention and stability of lipidized Bowman-Birk protease inhibitor in mice. Int J Pharm 204: 111-6 (2000).
79. T. Uchiyama, A. Kotani, H. Tatsumi, T. Kishida, A. Okamoto, N. Okada, M. Murakami, T. Fujita, Y. Fujiwara, Y. Kiso, S. Muranishi, and A. Yamamoto. Development of novel lipophilic derivatives of DADLE (leucine enkephalin analogue): intestinal permeability characateristics of DADLE derivatives in rats. Pharm Res 17: 1461-7 (2000).
80. E. Yodoya, K. Uemura, T. Tenma, T. Fujita, M. Murakami, A. Yamamoto, and S. Muranishi. Enhanced permeability of tetragastrin across the rat intestinal membrane and its reduced degradation by acylation with various fatty acids. J Pharmacol Exp Ther 271: 1509-13 (1994).
81. S. Havelund, A. Plum, U. Ribel, I. Jonassen, A. Volund, J. Markussen, and P. Kurtzhals. The mechanism of protraction of insulin detemir, a long-acting, acylated analog of human insulin. Pharm Res 21: 1498-504 (2004).
82. A. V. Kabanov, A. V. Ovcharenko, N. S. Melik-Hubarov, A. I. Bannikov, V. Alakhov, V. I. Kiselev, P. G. Sveshnikov, O. I. Kiselev, A. V. Levashov, and E. S. Severin. Fatty acid acylated antibodies against virus suppress its reproduction in cells. FEBS Lett 250: 238-40 (1989).
83. J. Wang, D. Chow, H. Heiati, and W. C. Shen. Reversible lipidization for the oral delivery of salmon calcitonin. J Control Release 88: 369-80 (2003).
84. D. Shah and W. C. Shen. The establishment of polarity and enhanced transcytosis of transferrin receptors in enterocyte-like Caco-2 cells. J Drug Target 2: 93-9 (1994).
85. P. R. Azari and R. E. Feeney. Resistance of metal complexes of conalbumin and transferrin to proteolysis and to thermal denaturation. J Biol Chem 232: 293-302 (1958).
86. A. Widera, F. Norouziyan, and W. C. Shen. Mechanisms of TfRmediated transcytosis and sorting in epithelial cells and applications toward drug delivery. Adv Drug Deliv Rev 55: 1439-66 (2003).
87. D. Shah and W. C. Shen. Transcellular delivery of an insulintransferrin conjugate in enterocyte-like Caco-2 cells. J Pharm Sci 85: 1306-11 (1996).
88. C. Q. Xia, J. Wang, and W. C. Shen. Hypoglycemic effect of insulin-transferrin conjugate in streptozotocininduced diabetic rats J Pharmacol Exp Ther 295: 594-600 (2000).
89. Y. Bai, D. K. Ann, and W. C. Shen. Recombinant granulocyte colony-stimulating factor-transferrin fusion protein as an oral myelopoietic agent. Proc Natl Acad Sci U S A 102: 7292-6 (2005).
90. Y. Bai and W. C. Shen. Improving the oral efficacy of recombinant granulocyte colony-stimulating factor and transferrin fusion protein by spacer optimization. Pharm Res 23: 2116-21 (2006).
91. N. J. Kavimandan, E. Losi, J. J. Wilson, J. S. Brodbelt, and N. A. Peppas. Synthesis and Characterization of Insulin-Transferrin Conjugates. Bioconjug Chem 17: 1376-1384 (2006).
92. P. R. Beauchesne, N. S. Chung, and K. M. Wasan. Cyclosporine A: a review of current oral and intravenous delivery systems. Drug Dev Ind Pharm 33: 211-20 (2007).
93. S. J. Shire, Z. Shahrokh, and J. Liu. Challenges in the development of high protein concentration formulations. J Pharm Sci 93: 1390-402 (2004).
94. T. W. Ho, L. K. Mannix, X. Fan, C. Assaid, C. Furtek, C. J. Jones, C. R. Lines, and A. M. Rapoport. Randomized controlled trial of an oral CGRP antagonist, MK-0974, in acute treatment of migraine.