Why most oral insulin formulations do not reach clinical trials

Therapeutic Delivery

Volumn 6, Issue 8, 2015, Pages 973-987

  Lopes, Marlene ^a,b   Simões, Susana ^a,b   Veiga, Francisco ^a,b   Seiça, Raquel ^c   Ribeiro, António ^b,d  

^a UNIVERSITY OF COIMBRA   (Portugal)

^b UNIVERSITY OF COIMBRA   (Portugal)

^c UNIVERSITY OF COIMBRA   (Portugal)

^d UNIVERSITY OF PORTO   (Portugal)

Author keywords

[No Author keywords available]

Indexed keywords

INSULIN; LIPOSOME; NANOPARTICLE; SOLID LIPID NANOPARTICLE; ANTIDIABETIC AGENT; DRUG CARRIER;

CLINICAL TRIAL (TOPIC); COST BENEFIT ANALYSIS; DRUG BIOAVAILABILITY; DRUG FORMULATION; DRUG INDUSTRY; DRUG MARKETING; HUMAN; HYDROGEL; MICELLE; NANOFORMULATION; NANOTECHNOLOGY; NONHUMAN; POLYMERIZATION; PRIORITY JOURNAL; REVIEW; SCALE UP; DIABETES MELLITUS; MEDICINAL CHEMISTRY; ORAL DRUG ADMINISTRATION;

ADMINISTRATION, ORAL; CHEMISTRY, PHARMACEUTICAL; CLINICAL TRIALS AS TOPIC; DIABETES MELLITUS; DRUG CARRIERS; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN;

EID: 84945585107     PISSN: 20415990     EISSN: 20416008     Source Type: Journal    
DOI: 10.4155/TDE.15.47     Document Type: Review

References (111)

1. Mutalik M. Long-waited dream of oral insulin: where did we reach? Asian J. Pharm. Clin. Res. 4(2), 15-20 (2011).
2. Thatcher HS. The oral administration of insulin to rabbits. Exp. Biol. Med. 21(7), 368-370 (1924).
3. Kawada JUN, Tanaka N, Nozaki Y. No reduction of blood glucose in diabetic rats after oral administration of insulin liposomes prepared under acidic conditions. Endocrinol. Jpn 28(2), 235-238 (1981).
4. Diasome Pharmaceuticals. https://diasomepharmaceuticals.com/
5. Opie EL. On the relation of chronic interstitial pancreatitis to the islands of langerhans and to diabetes mellitus. J. Exp. Med. 5(4), 397-428 (1901).
6. Nobel Prize. www.nobelprize.org/educational/medicine/insulin
7. Berger M. Oral insulin 1922-1992: The history of continuous ambition and failure. In: Frontiers In Insulin Pharmacology. Berger M, Gries FA (Eds). Georg Thieme Verlag, Germany, 144-148 (1993).
8. Ryle AP, Sanger F, Smith LF, Kitai R. The disulphide bonds of insulin. Biochem J. 60(4), 541-556 (1955).
9. Ferguson JEA: US 3172814 A (1965).
10. Meienhofer J, Schnabel E, Bremer H et al. Synthese der Insulinketten und ihre Kombination zu insulinaktiven Praparaten. Z. Naturforsch B 18b, 1120 (1963).
11. Genentech. www.gene.com/
12. Pozzilli P, Pitocco D, Visalli N et al. No effect of oral insulin on residual beta-cell function in resent-onset Type I diabetes (the IMDIAB VII). Diabetologia 43(8), 1000-1004 (2000).
13. Generex biotechnology. www.generex.com
14. Lopez JE, Peppas NA. Cellular evaluation of insulin transmucosal delivery. J. Biomater. Sci. Polym. Ed. 15(4), 385-396 (2004).
15. Adams GG, Harding SE. Drug delivery systems for the treatment of diabetes mellitus: state of the art. Curr. Pharm. Design. 19(41), 7244-7263 (2013).
16. Plapied L, Duhem N, Des Rieux A, Préat V. Fate of polymeric nanocarriers for oral drug delivery. Curr. Opin. Colloid Interface Sci. 16(3), 228-237 (2011).
17. Gerich JE. Novel insulins: expanding options in diabetes management. Am. J. Med. 113(4), 308-316 (2002).
18. Owens D, Zinman B, Bolli G. Alternative routes of insulin delivery. Diabet. Med. 20(11), 886-898 (2003).
19. Hirai S, Ikenaga T, Matsuzawa T. Nasal absorption of insulin in dogs. Diabetes 27, 296-299 (1978).
20. Brange J, Langkjaer L. Insulin formulation and delivery. Pharm. Biotechnol. 10, 343-409 (1997).
21. Chen MC, Sonaje K, Chen KJ, Sung HW. A review of the prospects for polymeric nanoparticle platforms in oral insulin delivery. Biomaterials 32(36), 9826-9838 (2011).
22. Lopes MA, Abrahim BA, Seica R, Veiga F, Rodrigues CR, Ribeiro AJ. Intestinal uptake of insulin nanoparticles: facts or myths? Curr. Pharm. Biotechnol. 15(7), 629-638 (2014).
23. Ensign LM, Cone R, Hanes J. Oral drug delivery with polymeric nanoparticles: The gastrointestinal mucus barriers. Adv. Drug Deliv. Rev. 64, 557-570 (2012).
24. Davis ME, Chen Z, Shin DM. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat. Rev. Drug Discov. 7(9), 771-782 (2008).
25. Vauthier C, Bouchemal K. Processing and scale-up of polymeric nanoparticles. In: Intracellular Delivery. Prokop A (Ed.). Springer, The Netherlands, 433-456 (2011).
26. Raghava Srivalli KM, Mishra B. Drug nanocrystals: A way toward scale-up. Saudi Pharm. J. doi:10.1016/j. jsps.2014.04.007 (2014).
27. Galindo-Rodríguez SA, Puel F, Briançon S, Allémann E, Doelker E, Fessi H. Comparative scale-up of three methods for producing ibuprofen-loaded nanoparticles. Eur. J. Pharm. Sci. 25(4-5), 357-367 (2005).
28. Ranjan A, Mukerjee A, Helson L, Vishwanatha J. Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapy. J. Nanobiotechnol. 10(1), 38 (2012).
29. Xiliang Q, Yang C, Tiesong L et al. Large-scale synthesis of silver nanoparticles by aqueous reduction for lowtemperature sintering bonding. J. Nanomater. 2014 1-8 (2014).
30. Rietscher R, Thum C, Lehr C-M, Schneider M. Semiautomated nanoprecipitation-system-an option for operator independent, scalable and size adjustable nanoparticle synthesis. Pharm. Res. 32, 1859-1863 (2014).
31. Levin M. Pharmaceutical process scale-up. Marcel Dekker, NY, USA (2002).
32. Song L, Zhi Z-L, Pickup JC. Nanolayer encapsulation of insulin-chitosan complexes improves efficiency of oral insulin delivery. Int. J. Nanomedicine 9, 2127-2136 (2014).
33. Fonte P, Araújo F, Reis S, Sarmento B. Oral insulin delivery: how far are we? J. Diabetes. Sci. Technol. 7(2), 520-531 (2013).
34. Zijlstra E, Heinemann L, Plum-Mörschel L. Oral insulin reloaded: A structured approach. J. Diabetes. Sci. Technol. 8(3), 458-465 (2014).
35. Leader B, Baca Q J, Golan DE. Protein therapeutics: A summary and pharmacological classification. Nat. Rev. Drug Discov. 7(1), 21-39 (2008).
36. Wong TW. Design of oral insulin delivery systems. J. Drug Target. 18(2), 79-92 (2010).
37. Lopes MA, Abrahim BA, Cabral LM et al. Intestinal absorption of insulin nanoparticles: contribution of M cells. Nanomedicine 10(6), 1139-1151 (2014).
38. Carino GP, Jacob JS, Mathiowitz E. Nanosphere based oral insulin delivery. J. Control. Release 65(1-2), 261-269 (2000).
39. Reis CP, Neufeld RJ, Ribeiro AJ, Veiga F. Nanoencapsulation II. Biomedical applications and current status of peptide and protein nanoparticulate delivery systems. Nanomedicine 2(2), 53-65 (2006).
40. Zhang X, Qi J, Lu Y, He W, Li X, Wu W. Biotinylated liposomes as potential carriers for the oral delivery of insulin. Nanomedicine 10(1), 167-176 (2014).
41. Almeida AJ, Souto E. Solid lipid nanoparticles as a drug delivery system for peptides and proteins. Adv. Drug Deliv. Rev. 59(6), 478-490 (2007).
42. Yun Y, Cho YW, Park K. Nanoparticles for oral delivery: targeted nanoparticles with peptidic ligands for oral protein delivery. Adv. Drug Deliv. Rev. 65(6), 822-832 (2013).
43. Sarmento B, Martins S, Ferreira D, Souto EB. Oral insulin delivery by means of solid lipid nanoparticles. Int. J. Nanomedicine 2(4), 743-749 (2007).
44. Pan Y, Li Y-J, Zhao H-Y et al. Bioadhesive polysaccharide in protein delivery system: chitosan nanoparticles improve the intestinal absorption of insulin in vivo. Int. J. Pharm. 249(1-2), 139-147 (2002).
45. Peppas NA. Devices based on intelligent biopolymers for oral protein delivery. Int. J. Pharm. 277(1-2), 11-17 (2004).
46. Teply BA, Tong R, Jeong SY et al. The use of chargecoupled polymeric microparticles and micromagnets for modulating the bioavailability of orally delivered macromolecules. Biomaterials 29(9), 1216-1223 (2008).
47. Morishita M, Goto T, Takayama K, Peppas NA. Oral insulin delivery systems based on complexation polymer hydrogels. J. Drug Deliv. Sci. Technol. 16(1), 19-24 (2006).
48. Jafari B, Rafie F, Davaran S. Preparation and characterization of a novel smart polymeric hydrogel for drug delivery of insulin. BioImpacts 1(2), 135-143 (2011).
49. Li CL, Deng YJ. Oil-based formulations for oral delivery of insulin. J. Pharm. Pharmacol. 56(9), 1101-1107 (2004).
50. Liu G, Ma R, Ren J et al. A glucose-responsive complex polymeric micelle enabling repeated on-off release and insulin protection. Soft Matter 9(5), 1636-1644 (2013).
51. Zhang G, Zhang X, Shen H, Yang J, Yang J. Smarter glucose-sensitivity of polymeric micelles formed from phenylborate ester-co-pyrenylboronic ester for insulin delivery at physiological pH. RSC Adv. 4(91), 49964-49973 (2014).
52. Pardakhty A, Varshosaz J, Rouholamini A. In vitro study of polyoxyethylene alkyl ether niosomes for delivery of insulin. Int. J. Pharm. 328(2), 130-141 (2007).
53. Zhang N, Ping QN, Huang GH, Xu WF. Investigation of lectin-modified insulin liposomes as carriers for oral administration. Int. J. Pharm. 294(1-2), 247-259 (2005).
54. Mahale NB, Thakkar PD, Mali RG, Walunj DR, Chaudhari SR. Niosomes: novel sustained release nonionic stable vesicular systems-an overview. Adv. Colloid Interface Sci. 183-184, 46-54 (2012).
55. Liu J, Gong T, Wang C, Zhong Z, Zhang Z. Solid lipid nanoparticles loaded with insulin by sodium cholatephosphatidylcholine-based mixed micelles: preparation and characterization. Int. J. Pharm. 340(1-2), 153-162 (2007).
56. Fonte P, Nogueira T, Gehm C, Ferreira D, Sarmento B. Chitosan-coated solid lipid nanoparticles enhance the oral absorption of insulin. Drug Deliv. Transl. Res. 1(4), 299.308 (2011).
57. Zhang N, Ping Q, Huang G, Xu W, Cheng Y, Han X. Lectin-modified solid lipid nanoparticles as carriers for oral administration of insulin. Int. J. Pharm. 327(1.2), 153.159 (2006).
58. Morishita M, Goto T, Peppas NA et al. Mucosal insulin delivery systems based on complexation polymer hydrogels: effect of particle size on insulin enteral absorption. J. Control. Release 97(1), 115.124 (2004).
59. Norris DA, Puri N, Sinko PJ. The effect of physical barriers and properties on the oral absorption of particulates. Adv. Drug Deliv. Rev. 34(2.3), 135.154 (1998).
60. Damge C, Reis CP, Maincent P. Nanoparticle strategies for the oral delivery of insulin. Expert Opin. Drug Deliv. 5(1), 45.68 (2008).
61. Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf. B 75(1), 1.18 (2010).
62. Ponchel G, Irache J-M. Specific and non-specific bioadhesive particulate systems for oral delivery to the gastrointestinal tract. Adv. Drug Deliv. Rev. 34(2.3), 191.219 (1998).
63. Ma Z, Lim TM, Lim L-Y. Pharmacological activity of peroral chitosan.insulin nanoparticles in diabetic rats. Int. J. Pharm. 293(1.2), 271.280 (2005).
64. Sarmento B, Ribeiro A, Veiga F, Ferreira D, Neufeld R. Oral Bioavailability of insulin contained in polysaccharide nanoparticles. Biomacromolecules 8(10), 3054.3060 (2007).
65. Foss AC, Goto T, Morishita M, Peppas NA. Development of acrylic-based copolymers for oral insulin delivery. Eur. J. Pharm. Biopharm. 57(2), 163.169 (2004).
66. Chalasani KB, Russell-Jones GJ, Jain AK, Diwan PV, Jain SK. Effective oral delivery of insulin in animal models using vitamin B12-coated dextran nanoparticles. J. Control. Release 122(2), 141.150 (2007).
67. Radwan MA, Aboul-Enein HY. The effect of oral absorption enhancers on the in vivo performance of insulinloaded poly(ethylcyanoacrylate) nanospheres in diabetic rats. J. Microencapsul. 19(2), 225.235 (2002).
68. Radwan MA. Enhancement of absorption of insulin-loaded polyisobutylcyanoacrylate nanospheres by sodium cholate after oral and subcutaneous administration in diabetic rats. Drug Dev. Ind. Pharm. 27(9), 981.989 (2001).
69. Ubaidulla U, Sultana Y, Ahmed FJ, Khar RK, Panda AK. Chitosan phthalate microspheres for oral delivery of insulin: preparation, characterization, and In vitro evaluation. Drug Deliv. 14(1), 19.23 (2007).
70. Hua Q. Insulin: A small protein with a long journey. Protein Cell 1(6), 537.551 (2010).
71. Rajeswari TS. Non invasive insulins: advanced insulin therapy over this decade. JAPS 1(8), 12.20 (2011).
72. Bajpai AK, Shukla SK, Bhanu S, Kankane S. Responsive polymers in controlled drug delivery. Prog. Polym. Sci. 33(11), 1088.1118 (2008).
73. Peppas NA, Wood KM, Blanchette JO. Hydrogels for oral delivery of therapeutic proteins. Expert Opin. Biol. Ther. 4(6), 881.887 (2004).
74. Chaturvedi K, Ganguly K, Nadagouda MN, Aminabhavi TM. Polymeric hydrogels for oral insulin delivery. J. Control. Release 165(2), 129.138 (2013).
75. Wood KM, Stone GM, Peppas NA. The effect of complexation hydrogels on insulin transport in intestinal epithelial cell models. Acta Biomater. 6(1), 48.56 (2010).
76. Sajeesh S, Bouchemal K, Marsaud V, Vauthier C, Sharma CP. Cyclodextrin complexed insulin encapsulated hydrogel microparticles: an oral delivery system for insulin. J. Control. Release 147(3), 377.384 (2010).
77. Lakkakula JR, Macedo Krause RW. A vision for cyclodextrin nanoparticles in drug delivery systems and pharmaceutical applications. Nanomedicine 9(6), 877.894 (2014).
78. Simoes SMN, Veiga F, Torres-Labandeira JJ, Ribeiro ACF, Concheiro A, Alvarez-Lorenzo C. Syringeable self-assembled cyclodextrin gels for drug delivery. Curr. Top. Med. Chem. 14(4), 494.509 (2014).
79. Simoes SMN, Rey-Rico A, Concheiro A, Alvarez-Lorenzo C. Supramolecular cyclodextrin-based drug nanocarriers. Chem. Commun. 51(29), 6275.6289 (2015).
80. Sajeesh S, Sharma CP. Cyclodextrin.insulin complex encapsulated polymethacrylic acid based nanoparticles for oral insulin delivery. Int. J. Pharm. 325(1.2), 147.154 (2006).
81. Zhang L, Zhu W, Song L et al. Effects of hydroxylpropyl-cyclodextrin on in vitro insulin stability. Int. J. Mol. Sci. 10(5), 2031.2040 (2009).
82. Qiu Y, Park K. Environment-sensitive hydrogels for drug delivery. Adv. Drug Deliv. Rev. 53(3), 321.339 (2001).
83. Laroui H, Sitaraman SV, Merlin D. Gastrointestinal delivery of anti-inflammatory nanoparticles. Methods Enzymol. 509, 101.125 (2012).
84. Simoes SM, Figueiras AR, Veiga F, Concheiro A, Alvarez-Lorenzo C. Polymeric micelles for oral drug administration enabling locoregional and systemic treatments. Expert Opin. Drug Deliv. 12(2), 297.318 (2015).
85. Lu Y, Park K. Polymeric micelles and alternative nanonized delivery vehicles for poorly soluble drugs. Int. J. Pharm. 453(1), 198-214 (2013).
86. Yokoyama M, Opanasopit P, Okano T, Kawano K, Maitani Y. Polymer design and incorporation methods for polymeric micelle carrier system containing water-insoluble anticancer agent camptothecin. J. Drug. Target. 12(6), 373-384 (2004).
87. Li P, Nielsen HM, Müllertz A. Oral delivery of peptides and proteins using lipid-based drug delivery systems. Expert Opin. Drug Deliv. 9(10), 1289-1304 (2012).
88. Fricker G, Kromp T, Wendel A et al. Phospholipids and lipidbased formulations in oral drug delivery. Pharm. Res. 27(8), 1469-1486 (2010).
89. Pardakhty A, Moazeni E, Varshosaz J, Hajhashemi V, Rouholamini Najafabadi A. Pharmacokinetic study of niosome-loaded insulin in diabetic rats. Daru 19(6), 404-411 (2011).
90. Li Z, Chen J, Sun W, Xu Y. Investigation of archaeosomes as carriers for oral delivery of peptides. Biochem. Biophys. Res. Commun. 394(2), 412-417 (2010).
91. Müller RH, Lippacher A, Gohala S. Solid lipid nanoparticles (SLN) as carrier system for the controlled release of drugs. In: Handbook of Pharmaceutical Controlled Release Technology. Wise DL (Ed.). Marcel Dekker, NY, USA, 377-391 (2000).
92. Müller RH, Mäder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery-A review of the state of the art. Eur. J. Pharm. Biopharm. 50(1), 161-177 (2000).
93. Fonte P, Andrade F, Araújo F, Andrade C, Neves JD, Sarmento B. Chitosan-coated solid lipid nanoparticles for insulin delivery. Methods Enzymol. 508, 295-314 (2012).
94. Wirth M, Hamilton G, Gabora F. Lectin-mediated drug targeting: quantification of binding and internalization of wheat germ agglutinin and solatium tuberosum lectin using Caco-2 and HT-29 cells. J. Drug. Target. 6(2), 95-104 (1998).
95. Zhang X, Sun M, Zheng A, Cao D, Bi Y, Sun J. Preparation and characterization of insulin-loaded bioadhesive PLGA nanoparticles for oral administration. Eur. J. Pharm. Sci. 45(5), 632-638 (2012).
96. Prusty AK, Sahu SK. Development and evaluation of insulin incorporated nanoparticles for oral administration. ISRN Nanotechnology 2013, 6 (2013).
97. Elsayed A, Remawi MA, Qinna N, Farouk A, Badwan A. Formulation and characterization of an oily-based system for oral delivery of insulin. Eur. J. Pharm. Biopharm. 73(2), 269-279 (2009).
98. Quellhorst E. Insulin therapy during peritoneal dialysis. Pros and cons of various forms of administration. J. Am. Soc. Nephrol. 13(Suppl. 1), S92-S96 (2002).
99. Heinemann L, Jacques Y. Oral insulin and buccal insulin: A critical reappraisal. J. Diabetes Sci. Technol. 3(3), 568-584 (2009).
100. Arbit E, Kidron M. Oral Insulin: The rationale for this approach and current developments. J. Diabetes Sci. Technol. 3(3), 562-567 (2009).
101. Giovannucci E. Insulin and colon cancer. Cancer Causes Control 6, 164-179 (1995).
102. Antunes F, Andrade F, Araújo F, Ferreira D, Sarmento B. Establishment of a triple co-culture in vitro cell models to study intestinal absorption of peptide drugs. Eur. J. Pharm. Biopharm. 83(3), 427-435 (2013).
103. Kanzarkar M, Pathak PP, Vaidya M, Brumlik C, Choudhury A. Oral insulin-delivery system for diabetes mellitus. Pharm. Pat. Anal. 4(1), 29-36 (2015).
104. Navgire SD, Satpute AS, Pandey S, Patil AT. Recent patents on oral insulin delivery. Recent Pat. Drug Deliv. Formul. 8(3), 202-205 (2014).
105. Muheem A, Shakeel F, Jahangir MA et al. A review on the strategies for oral delivery of proteins and peptides and their clinical perspectives. Saudi Pharm. J. doi:10.1016/j. jsps.2014.06.004 (2014).
106. Oramed Pharmaceuticals. www.oramed.com/
107. Biocon. www.biocon.com/
108. Merrion Pharmaceuticals. www.merrionpharma.com/
109. Emisphere. www.emisphere.com/
110. Diabetology. www.diabetology.co.uk/
111. Oshadi drug administration. https://clinicaltrials.gov/ct2/show/NCT01973920