Noninjectable methods of insulin administration

Drugs of Today

Volumn 42, Issue 6, 2006, Pages 405-424

  Cernea, Simona ^a   Raz, Itamar ^b  

^a Och Spine at New York Presbyterian Hospitals   (United States)

^b HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

APROTININ; HEXYL INSULIN MONOCONJUGATE 2; INSULIN; INSULIN ZINC SUSPENSION; METFORMIN; PROTEINASE INHIBITOR; RECOMBINANT HUMAN INSULIN; ROSIGLITAZONE; SOYBEAN TRYPSIN INHIBITOR; SULFONYLUREA; TRANSFERSULIN;

ANXIETY; AREA UNDER THE CURVE; BLISTER PACK; CLINICAL TRIAL; COST EFFECTIVENESS ANALYSIS; DIABETES MELLITUS; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG CONTRAINDICATION; DRUG COST; DRUG DELIVERY SYSTEM; DRUG FORMULATION; DRUG MECHANISM; DRUG SAFETY; DRUG TRANSPORT; GLUCOSE ABSORPTION; GLUCOSE BLOOD LEVEL; GLYCEMIC CONTROL; HUMAN; HYPOGLYCEMIA; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN INFUSION; INSULIN RELEASE; INSULIN SENSITIVITY; INSULIN TREATMENT; IONTOPHORESIS; LIFESTYLE; NON INSULIN DEPENDENT DIABETES MELLITUS; NOSE IRRITATION; NOSE MUCOSA; PATHOGENESIS; REVIEW; SIDE EFFECT; SKIN PERMEABILITY; THERMODYNAMICS; WEIGHT GAIN;

DIABETES MELLITUS; DRUG ADMINISTRATION ROUTES; HUMANS; INSULIN; PATIENT SATISFACTION;

EID: 33746264036     PISSN: 16993993     EISSN: 16994019     Source Type: Journal    
DOI: 10.1358/dot.2006.42.6.985632     Document Type: Review

References (176)

1. Zimmet, P., Alberti, K.G., Shaw, J. Global and societal implications of the diabetes epidemic. Nature 2001, 414: 782-7.
2. Wild, S., Roglic, G., Green, A., Sicree, R., King, H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 2004, 27: 1047-53.
3. Rolla, A. The pathophysiological basis for intensive insulin replacement. Int J Obes Relat Metab Disord 2004, 28 (Suppl. 2): S3-7.
4. Polonsky, K.S., Given, B.D., Hirsch, L.J. et al. Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus. N Engl J Med 1988, 318: 1231-9.
5. Bretzel, R.G. Intensive insulin regimens: Evidence for benefit. Int J Obes Relat Metab Disord 2004, 28 (Suppl. 2): S8-13
6. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993, 329: 977-86.
7. 1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes 1995, 44: 968-83.
8. The Diabetes Control and Complications Trial/ Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA 2002, 287: 2563-9.
9. The Diabetes Control and Complications Trial/ Epidemiology of Diabetes Interventions and Complications Research Group. Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: The Epidemiology of Diabetes Interventions and Complications (EDIC) study. JAMA 2003, 290: 2159-67.
10. The Diabetes Control and Complications Trial/ Epidemiology of Diabetes Interventions and Complications Research Group. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N Engl J Med 2000, 342: 381-9.
11. Ohkubo, Y., Kishikawa, H., Araki, E. et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: A randomized prospective 6-year study. Diabetes Res Clin Pract 1995, 28: 103-17.
12. Shichiri, M., Kishikawa, H., Ohkubo, Y., Wake, N. Long-term results of the Kumamoto Study on optimal diabetes control in type 2 diabetic patients. Diabetes Care 2000, 23 (Suppl. 2): B21-9.
13. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998, 352: 837-53.
14. Stratton, I.M., Adler, A.I., Neil, H.A. et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study. BMJ 2000, 321: 405-12.
15. Rizza, R.A., Gerich, J.E., Haymond, M.W. et al. Control of blood sugar in insulin-dependent diabetes: Comparison of an artificial endocrine pancreas, continuous subcutaneous insulin infusion, and intensified conventional insulin therapy. N Engl J Med. 1980, 303: 1313-8.
16. Cefalu, W.T. Evolving strategies for insulin delivery and therapy. Drugs 2004, 64: 1149-61.
17. Lauritzen, T., Faber, O.K., Binder, C. Variation in 1251-insulin absorption and blood glucose concentration. Diabetologia 1979, 17: 291-5.
18. Binder, C., Lauritzen, T., Faber, O., Pramming, S. Insulin pharmacokinetics. Diabetes Care 1984, 7: 188-99.
19. Galloway, J.A., Spradlin, C.T., Nelson, R.L., Wentworth, S.M., Davidson, J.A., Swarner, J.L. Factors influencing the absorption, serum insulin concentration, and blood glucose responses after injections of regular insulin and various insulin mixtures. Diabetes Care 1981, 4: 366-76.
20. Cefalu, WT, Skyler, J.S., Kourides, I.A. et al.; Inhaled Insulin Study Group. Inhaled human insulin treatment in patients with type 2 diabetes mellitus. Ann Intern Med 2001, 134: 203-7.
21. Rungby, J., Brock, B., Schmitz, O. New strategies in insulin treatment: Analogues and noninvasive routes of administration. Fundam Clin Pharmacol 2005, 19: 127-32.
22. Gerich, J.E. Novel insulins: Expanding options in diabetes management. Am J Med 2002, 113: 308-16.
23. Korytkowski, M. When oral agents fail: Practical barriers to starting insulin. Int J Obes Relat Metab Disord 2002, 26 (Suppl. 3): S18-24.
24. Turner, R.C., Cull, C.A., Frighi, V., Holman, R.R. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: Progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA 1999, 281: 2005-12.
25. Heine, R.J. Unlocking the opportunity of tight glycaemic control. Promise ahead: The role of inhaled insulin in clinical practice. Diabetes Obes Metab 2005, 7 (Suppl. 1): S19-23.
26. Peyrot, M., Rubin, R.R., Lauritzen, T. et al.; The International DAWN Advisory Panel. Resistance to insulin therapy among patients and providers: Results of the cross-national Diabetes Attitudes, Wishes and Needs (DAWN) study. Diabetes Care 2005, 28: 2673-9.
27. Wallace, T.M., Matthews, D.R. Poor glycaemic control in type 2 diabetes: A conspiracy of disease, suboptimal therapy and attitude. QJM 2000, 93: 369-74.
28. Ratzmann, K.P. The psychological aspects of diabetics with the secondary failure of sulfonylurea therapy. (In German.) Dtsch Med Wochenschr 1991, 116: 87-90.
29. Hunt, L.M., Valenzuela, M.A., Pugh, J.A. NID-DM patients' fears and hopes about insulin therapy. The basis of patient reluctance. Diabetes Care 1997, 20: 292-8.
30. Zambanini, A., Newson, R.B., Maisey, M., Feher, M.D. Injection-related anxiety in insulin-treated diabetes. Diabetes Res Clin Pract 1999, 46: 239-46.
31. Peyrot, M., Rubin, R.R., Lauritzen, T., Snoek, F.J., Matthews, D.R., Skovlund, S.E. Psychosocial problems and barriers to improved diabetes management: Results of the Cross-National Diabetes Attitudes, Wishes and Needs (DAWN) Study. Diabet Med 2005, 22: 1379-85.
32. Mollema, E.D., Snoek, F.J., Ader, H.J., Heine, R.J., van der Ploeg, H.M. Insulin-treated diabetes patients with fear of self-injecting or fear of self-testing: Psychological comorbidity and general well-being. J Psychosom Res 2001, 51: 665-72.
33. Mollema, E.D., Snoek, F.J., Pouwer, F., Heine, R.J., van der Ploeg, H.M. Diabetes Fear of Injecting and Self-Testing Questionnaire: A psychometric evaluation. Diabetes Care 2000, 23: 765-9.
34. Mollema, E.D., Snoek, F.J., Heine, R.J., van der Ploeg, H.M. Phobia of self-injecting and self-testing in insulin-treated diabetes patients: Opportunities for screening. Diabet Med 2001, 18: 671-4.
35. Heinemann, L., Pfutzner, A., Heise, T. Alternative routes of administration as an approach to improve insulin therapy: Update on dermal, oral, nasal and pulmonary insulin delivery. Curr Pharm Des 2001, 7: 1327-51.
36. Barry, B.W. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci 2001, 14: 101-14.
37. Prausnitz, M.R., Mitragotri, S., Langer, R. Current status and future potential of transdermal drug delivery. Nat Rev Drug Discov 2004, 3: 115-24.
38. Kanikkannan, N., Kandimalla, K., Lamba, S.S., Singh, M. Structure-activity relationship of chemical penetration enhancers in transdermal drug delivery. Curr Med Chem 2000, 7: 593-608.
39. Cevc, G. Transfersomes, liposomes and other lipid suspensions on the skin: Permeation enhancement, vesicle penetration, and transdermal drug delivery. Crit Rev Ther Drug Carrier Syst 1996, 13: 257-388.
40. Cevc, G. Transdermal drug delivery of insulin with ultradeformable carriers. Clin Pharmacokinet 2003, 42: 461-74.
41. Cevc, G., Gebauer, D., Stieber, J., Schatzlein, A., Blume, G. Ultraflexible vesicles, transfersomes, have an extremely low pore penetration resistance and transport therapeutic amounts of insulin across the intact mammalian skin. Biochim Biophys Acta 1988, 1368: 201-15.
42. Godin, B., Touitou, E. Ethosomes: New prospects in transdermal delivery. Crit Rev Ther Drug Carrier Syst 2003, 20: 63-102.
43. King, M.J., Badea, I., Solomon, J., Kumar, P., Gaspar, K.J., Foldvari, M. Transdermal delivery of insulin from a novel biphasic lipid system in diabetic rats. Diabetes Technol Ther 2002, 4: 479-88.
44. King, M.J., Michel, D., Foldvari, M. Evidence for lymphatic transport of insulin by topically applied biphasic vesicles. J Pharm Pharmacol 2003, 55: 1339-44.
45. Curdy, C., Kalia, Y.N., Guy, R.H. Non-invasive assessment of the effects of iontophoresis on human skin in-vivo. J Pharm Pharmacol 2001, 53: 769-77.
46. Kalia, Y.N., Naik, A., Garrison, J., Guy, R.H. lontophoretic drug delivery. Adv Drug Deliv Rev 2004, 56: 619-58.
47. Pillai, O., Kumar, N., Dey, C.S., Borkute, Sivaprasad, N., Panchagnula, R. Transdermal iontophoresis of insulin: III. Influence of electronic parameters. Methods Find Exp Clin Pharmacol 2004, 26: 399-408.
48. Langkjaer, L., Brange, J., Grodsky, G.M., Guy, R.H. Iontophoresis of monomeric insulin analogues in vitro: Effects of insulin charge and skin pretreatment. J Control Release 1998, 51: 47-56.
49. Kanikkannan, N., Singh, J., Ramarao, P. Transdermal iontophoretic delivery of bovine insulin and monomeric human insulin analogue. J Control Release 1999, 59: 99-105.
50. Pillai, O., Panchagnula, R. Transdermal iontophoresis of insulin. V. Effect of terpenes. J Control Release 2003, 88: 287-96.
51. Pillai, O., Nair, V., Panchagnula, R. Transdermal iontophoresis of insulin: IV. Influence of chemical enhancers. Int J Pharm 2004, 269: 109-20.
52. Rastogi, S.K., Singh, J. Transepidermal transport enhancement of insulin by lipid extraction and iontophoresis. Pharm Res 2002, 19: 427-33.
53. Machet, L., Boucaud, A. Phonophoresis: Efficiency, mechanisms and skin tolerance. Int J Pharm 2002, 243: 1-15.
54. Mitragotri, S., Kost, J. Low-frequency sonophoresis: A review. Adv Drug Deliv Rev 2004, 56: 589-601.
55. Mitragotri, S., Blankschtein, D., Langer, R. Ultrasound-mediated transdermal protein delivery. Science 1995, 269: 850-3.
56. Boucaud, A., Garrigue, M.A., Machet, L., Vaillant, L., Patat, F. Effect of sonication parameters on transdermal delivery of insulin to hairless rats. J Control Release 2002, 81: 113-9.
57. Tachibana, K., Tachibana, S. Transdermal delivery of insulin by ultrasonic vibration. J Pharm Pharmacol 1991, 43: 270-1.
58. Smith, N.B., Lee, S., Shung, K.K. Ultrasound-mediated transdermal in vivo transport of insulin with low-profile cymbal arrays. Ultrasound Med Biol 2003, 29: 1205-10.
59. Smith, N.B., Lee, S., Maione, E., Roy, R.B., McElligott, S., Shung, K.K. Ultrasound-mediated transdermal transport of insulin in vitro through human skin using novel transducer designs. Ultrasound Med Biol. 2003, 29: 311-7.
60. Mitragotri, S., Kost, J. Low-frequency sonophoresis: A noninvasive method of drug delivery and diagnostics. Biotechnol Prog 2000, 16: 488-92.
61. Sen, A., Daly, M.E., Hui, S.W. Transdermal insulin delivery using lipid enhanced electroporation. Biochim Biophys Acta 2002, 1564: 5-8.
62. Lee, S., McAuliffe, D.J., Flotte, T.J., Kollias, N., Doukas, A.G. Photomechanical transdermal delivery: The effect of laser confinement. Lasers Surg Med 2001, 28: 344-7.
63. Mitragotri, S. Synergistic effect of enhancers for transdermal drug delivery. Pharm Res 2000, 17: 1354-9.
64. Turker, S., Onur, E., Ozer, Y. Nasal route and drug delivery systems. Pharm World Sci 2004, 26: 137-42.
65. Gizurarson, S., Bechgaard, E. Intranasal administration of insulin to humans. Diabetes Res Clin Pract 1991, 12: 71-84.
66. Owens, D.R., Zinman, B., Bolli, G. Alternative routes of insulin delivery. Diabet Med. 2003, 20: 886-98.
67. Gómez-Pèrez, F.J., Rull, J.A. Insulin therapy: Current alternatives. Arch Med Res 2005, 36: 258-72.
68. Merkus, F.W., Verhoef, J.C., Schipper, N.G., Marttin, E. Nasal mucociliary clearance as a factor in nasal drug delivery. Adv Drug Deliv Rev 1998, 29: 13-38.
69. Hilsted, J., Madsbad, S., Hvidberg, A. et al. Intranasal insulin therapy: The clinical realities. Diabetologia 1995, 38: 680-4.
70. Drejer, K., Vaag, A., Bech, K., Hansen, P., Sorensen, A.R., Mygind, N. Intranasal administration of insulin with phospholipid as absorption enhancer: Pharmacokinetics in normal subjects. Diabet Med 1992, 9: 335-40.
71. Jacobs, M.A., Schreuder, R.H., Jap-A-Joe, K., Nauta, J.J., Andersen, P.M., Heine, R.J. The pharmacodynamics and activity of intranasally administered insulin in healthy male volunteers. Diabetes 1993, 42: 1649-55.
72. Moses, A.C., Gordon, G.S., Carey, M.C., Flier, J.S. Insulin administered intranasally as an insulin-bile salt aerosol. Effectiveness and reproducibility in normal and diabetic subjects. Diabetes 1983, 32: 1040-7.
73. Gordon, G.S., Moses, A.C., Silver, R.D., Flier, J.S., Carey, M.C. Nasal absorption of insulin: Enhancement by hydrophobic bile salts. Proc Natl Acad Sci USA 1985, 82: 7419-23.
74. Nolte, M.S., Taboga, C., Salamon, E. et al. Biological activity of nasally administered insulin in normal subjects. Horm Metab Res 1990, 22: 170-4.
75. Coates, P.A., Ismail, I.S., Luzio, S.D. et al. Intranasal insulin: The effects of three dose regimens on postprandial glycaemic profiles in type II diabetic subjects. Diabet Med 1995, 12: 235-9.
76. Pontiroli, A.E., Alberetto, M., Secchi, A., Dossi, G., Bosi, I., Pozza, G. Insulin given intranasally induces hypoglycaemia in normal and diabetic subjects. Br Med J (Clin Res Ed) 1982, 284: 303-6.
77. Salzman, R., Manson, J.E., Gritting, G.T. et al. Intranasal aerosolized insulin. Mixed-meal studies and long-term use in type I diabetes. N Engl J Med 1985, 312: 1078-84.
78. Kimmerle, R., Griffing, G., McCall, A., Ruderman, N.B., Stoltz, E., Melby, J.C. Could intranasal insulin be useful in the treatment of non-insulin-dependent diabetes mellitus? Diabetes Res Clin Pract 1991, 13: 69-75.
79. Bruce, D.G., Chisholm, D.J., Storlien, L.H., Borkman, M., Kraegen, E.W. Meal-time intranasal insulin delivery in type 2 diabetes. Diabet Med 1991, 8: 366-70.
80. Frauman, A.G., Cooper, M.E., Parsons, B.J., Jerums, G., Louis, W.J. Long-term use of intranasal insulin in insulin-dependent diabetic patients. Diabetes Care 1987, 10: 573-8.
81. Lalej-Bennis, D., Boillot, J., Bardin, C. et al. Six-month administration of gelified intranasal insulin in 16 type 1 diabetic patients under multiple injections: Efficacy vs. subcutaneous injections and local tolerance. Diabetes Metab 2001, 27: 372-7.
82. Lalej-Bennis, D., Boillot, J., Bardin, C. et al. Efficacy and tolerance of intranasal insulin administered during 4 months in severely hyperglycaemic type 2 diabetic patients with oral drug failure: A cross-over study. Diabet Med 2001, 18: 614-8.
83. Valensi, P., Zirinis, P., Nicolas, P., Perret, G., Sandre-Banon, D., Attali, J.R. Effect of insulin concentration on bioavailability during nasal spray administration. Pathol Biol (Paris) 1996, 44: 235-40.
84. Pontiroli, A.E., Alberetto, M., Pajetta, E., Calderara, A., Pozza, G. Human insulin plus sodium glycocholate in a nasal spray formulation: Improved bioavailability and effectiveness in normal subjects. Diabetes Metab 1987, 13: 441-3.
85. Benedict, C., Dodt, C., Hallschmid, M. et al. Immediate but not long-term intranasal administration of insulin raises blood pressure in human beings. Metabolism 2005, 54: 1356-61.
86. Carino, G.P., Mathiowitz, E. Oral insulin delivery. Adv Drug Deliv Rev 1999, 35: 249-57.
87. Mesiha, M., Plakogiannis, F., Vejosoth, S. Enhanced oral absorption of insulin from desolvated fatty acid-sodium glycocholate emulsions. Int J Pharm 1994, 111: 213-6.
88. Mesiha, M.S., Ponnapula, S., Plakogiannis, F. Oral absorption of insulin encapsulated in artificial chyles of bile salts, palmitic acid and alpha-tocopherol dispersions. Int J Pharm 2002, 249: 1-5.
89. Ziv, E., Lior, O., Kidron, M. Absorption of protein via the intestinal wall. A quantitative model. Biochem Pharmacol 1987, 36: 1035-9.
90. Ziv, E., Kidron, M., Raz, I. et al. Oral administration of insulin in solid form to nondiabetic and diabetic dogs. J Pharm Sci 1994, 83: 792-4.
91. Bendayan, M., Ziv, E., Gingras, D., Ben-Sasson, R., Bar-On, H., Kidron, M. Biochemical and morpho-cytochemical evidence for the intestinal absorption of insulin in control and diabetic rats. Comparison between the effectiveness of duodenal and colon mucosa. Diabetologia 1994, 37: 119-26.
92. Lee, S., Lee, J., Lee, D.Y., Kim, S.K., Lee, Y., Byun, Y. A new drug carrier, Nalpha-deoxycholyl-L:-lysyl-methylester, for enhancing insulin absorption in the intestine. Diabetologia 2005, 48: 405-11.
93. Liang, J.F., Yang, V.C. Insulin-cell penetrating peptide hybrids with improved intestinal absorption efficiency. Biochem Biophys Res Commun 2005, 335: 734-8.
94. Kidron, M., Dinh, S., Menachem, Y. et al. A novel per-oral insulin formulation: Proof of concept study in non-diabetic subjects. Diabet Med 2004, 21: 354-57.
95. Asada, H., Douen, T., Waki, M. et al. Absorption characteristics of chemically modified-insulin derivatives with various fatty acids in the small and large intestine. J Pharm Sci 1995, 84: 682-7.
96. Gwinup, G., Elias, A.N., Domurat, E.S. Insulin and C-peptide levels following oral administration of insulin in intestinal-enzyme protected capsules. Gen Pharmacol 1991, 22: 243-6.
97. Gordon Still, J. Development of oral insulin: Progress and current status. Diabetes Metab Res Rev 2002, 18 (Suppl. 1): S29-37.
98. Wajcberg, E., Miyazaki, Y., Triplitt, C., Cersosimo, E., DeFronzo, R.A. Dose-response effect of a single administration of oral hexyl-insulin monoconjugate 2 in healthy nondiabetic subjects. Diabetes Care 2004, 27: 2868-73.
99. Clement, S., Still, J.G., Kosutic, G., McAllister, R.G. Oral insulin product hexyl-insulin monoconjugate 2 (HIM2) in type 1 diabetes mellitus: The glucose stabilization effects of HIM2. Diabetes Technol Ther 2002, 4: 459-66.
100. Kipnes, M., Dandona, P., Tripathy, D., Still, J.G., Kosutic, G. Control of postprandial plasma glucose by an oral insulin product (HIM2) in patients with type 2 diabetes. Diabetes Care 2003, 26: 421-6.
101. Kisel, M.A., Kulik, L.N., Tsybovsky, I.S. et al. Liposomes with phosphatidylethanol as a carrier for oral delivery of insulin: Studies in the rat. Int J Pharm 2001, 216: 105-14.
102. Choudhari, K.B., Labhasetwar, V., Dorle, A.K. Liposomes as a carrier for oral administration of insulin: Effect of formulation factors. J Microencapsul 1994, 11: 319-25.
103. Ramadas, M., Paul, W., Dileep, K.J., Anitha, Y., Sharma, C.P. Lipoinsulin encapsulated alginate-chitosan capsules: Intestinal delivery in diabetic rats. J Microencapsul 2000, 17: 405-11.
104. Whitehead, K., Shen, Z., Mitragotri, S. Oral delivery of macromolecules using intestinal patches: Applications for insulin delivery. J Control Release 2004, 98: 37-45.
105. Kimura, T., Sato, K., Sugimoto, K. et al. Oral administration of insulin as poly(vinyl alcohol)-gel spheres in diabetic rats. Biol Pharm Bull 1996, 19: 897-900.
106. Ramdas, M., Dileep, K.J., Anitha, Y., Paul, W., Sharma, C.P. Alginate encapsulated bioadhesive chitosan microspheres for intestinal drug delivery. J Biomater Appl 1999, 13: 290-6.
107. Musabayane, C.T., Munjeri, O., Bwititi, P., Osim, E.E. Orally administered, insulin-loaded amidated pectin hydrogel beads sustain plasma concentrations of insulin in streptozotocin-diabetic rats. J Endocrinol 2000, 164: 1-6.
108. Hosny, E.A., al-Shora, H.I., Elmazar, M.M. Effect of bioadhesive polymers, sodium salicylate, polyoxyethylene-9-lauryl ether, and method of preparation on the relative hypoglycemia produced by insulin enteric-coated capsules in diabetic beagle dogs. Drug Dev Ind Pharm 2002, 28: 563-70.
109. Marschutz, M.K., Bernkop-Schnurch, A. Oral peptide drug delivery: Polymer-inhibitor conjugates protecting insulin from enzymatic degradation in vitro. Biomaterials 2000, 21: 1499-1507.
110. Marschutz, M.K., Caliceti, P., Bernkop-Schnurch, A. Design and in vivo evaluation of an oral delivery system for insulin. Pharm Res 2000, 17: 1468-74.
111. Prego, C., Garcia, M., Torres, D., Alonso, M.J. Transmucosal macromolecular drug delivery. J Control Release 2005, 101: 151-62.
112. Mathiowitz, E., Jacob, J.S., Jong, Y.S. et al. Biologically erodable microspheres as potential oral drug delivery systems. Nature 1997, 386: 410-4.
113. López, J.E., Peppas, N.A. Effect of poly (ethylene glycol) molecular weight and microparticle size on oral insulin delivery from P(MAA-g-EG) microparticles. Drug Dev Ind Pharm 2004, 30: 497-504.
114. Chung, H., Kim, J., Um, J.Y., Kwon, I.C., Jeong, S.Y. Self-assembled "nanocubicle" as a carrier for peroral insulin delivery. Diabetologia 2002, 45: 448-51.
115. Vila, A., Sánchez, A., Tobio, M., Calvo, P., Alonso, M.J. Design of biodegradable particles for protein delivery. J Control Release 2002, 781: 5-24.
116. Senel, S., Kremer, M., Nagy, K., Squier, C. Delivery of bioactive peptides and proteins across oral (buccal) mucosa. Curr Pharm Biotechnol 2001, 2: 175-86.
117. Veuillez, F., Kalia, Y.N., Jacques, Y., Deshusses, J., Buri, P. Factors and strategies for improving buccal absorption of peptides. Eur J Pharm Biopharm 2001, 51: 93-109.
118. al-Achi, A., Greenwood, R. Buccal administration of human insulin in streptozocin-diabetic rats. Res Commun Chem Pathol Pharmacol 1993, 82: 297-306.
119. Oh, C.K., Ritschel, W.A. Absorption characteristics of insulin through the buccal mucosa. Methods Find Exp Clin Pharmacol 1990, 12: 275-9.
120. Zhang, J., Niu, S., Ebert, C., Stanley, T.H. An in vivo dog model for studying recovery kinetics of the buccal mucosa permeation barrier after exposure to permeation enhancers: Apparent evidence of effective enhancement without tissue damage. Int J Pharm 1994, 101: 1-173.
121. Oh, C.K., Ritschel, W.A. Biopharmaceutic aspects of buccal absorption of insulin. Methods Find Exp Clin Pharmacol 1990, 12: 205-12.
122. Aungst, B.J. Site-dependence and structure-effect relationships for alkylglycosides as transmucosal absorption promoters for insulin. Int J Pharm 1994, 105: 219-25.
123. Aungst, B.J., Rogers, N.J. Site dependence of absorption-promoting actions of laureth-9, Na salicylate, Na2EDTA, and aprotinin on rectal, nasal, and buccal insulin delivery. Pharm Res 1988, 5: 305-8.
124. Aungst, B.J. Structure/effect studies of fatty acid isomers as skin penetration enhancers and skin irritants. Pharm Res 1989, 6: 244-7.
125. Aungst, B.J., Rogers, N.J., Shefter, E. Comparison of nasal, rectal, buccal, sublingual and intramuscular insulin efficacy and the effects of a bile salt absorption promoter. J Pharmacol Exp Ther 1988, 244: 23-7.
126. Yang, T.Z., Wang, X.T., Van, X.Y., Zhang, Q. Phospholipid deformable vesicles for buccal delivery of insulin. Chem Pharm Bull (Tokyo) 2002, 50: 749-53.
127. Wang, W. Oral protein drug delivery. J Drug Target 1996, 4: 195-232.
128. Nagai, T. Adhesive topical drug delivery system. J Control Release 1985, 2: 121-34.
129. Modi, P., Mihic, M., Lewin, A. The evolving role of oral insulin in the treatment of diabetes using a novel RapidMist™ System. Diabetes Metab Res Rev 2002, 18 (Suppl. 1): S38-42.
130. Cernea, S., Kidron, M., Wohlgelernter, J., Modi, P., Raz, I. Comparison of pharmacokinetic and pharmacodynamic properties of single-dose oral insulin spray and subcutaneous insulin injection in healthy subjects using the euglycemic clamp technique. Clin Ther 2004, 26: 2084-91.
131. Cernea, S., Kidron, M., Wohlgelernter, J., Modi, P., Raz, I. Dose-response relationship of oral insulin spray in healthy subjects. Diabetes Care 2005, 28: 1353-7.
132. Cernea, S., Kidron, M., Wohlgelernter, J., Raz, I. Dose-response relationship of an oral insulin spray in six patients with type 1 diabetes: A single-center, randomized, single-blind, 5-way crossover study. Clin Ther 2005, 27: 1562-70.
133. Pozzilli, P., Manfrini, S., Costanza, F. et al. Biokinetics of buccal spray insulin in patients with type 1 diabetes. Metabolism 2005, 54: 930-4.
134. Guevara-Aguirre, J., Guevara, M., Saavedra, J., Mihic, M., Modi, P. Oral spray insulin in treatment of type 2 diabetes: A comparison of efficacy of the oral spray insulin (Oralin) with subcutaneous (SC) insulin injection, a proof of concept study. Diabetes Metab Res Rev 2004, 20: 472-8.
135. Guevara-Aguirre, J., Guevara, M., Saavedra, J., Mihic, M., Modi, P. Beneficial effects of addition of oral spray insulin (Oralin) on insulin secretion and metabolic control in subjects with type 2 diabetes mellitus suboptimally controlled on oral hypoglycemic agents. Diabetes Technol Ther 2004, 6: 1-8.
136. Raz, I., Dubinsky, A., Kidron, M., Wainstein, J. Addition of Oralin at mealtimes in subjects with type 2 diabetes maintained on glargine + metformin - A comparison with placebo. Diabetologia 2005, 48 (Suppl. 1): A298.
137. Gänsslen, M. Uber inhalation von insulin. Klin Wochenschr 1925, 4: 71.
138. Wigley, P.M., Londono, J.H., Scott, M.D., Wood, S.H., Shipp, J.C., Waldman, R.H. Insulin across respiratory mucosae by aerosol delivery. Diabetes 1971, 20: 552-6.
139. Laube, B.L., Georgeopolous, A., Adams, G.K. Preliminary study of the efficacy of insulin aerosol delivered by oral inhalation in diabetic patients. JAMA 1993, 269: 2106-9.
140. Patton, J.S. Mechanisms of macromolecule absorption by the lungs. Adv Drug Deliv Rev 1996, 19: 3-36.
141. Patton, J.S. Unlocking the opportunity of tight glycaemic control. Innovative delivery of insulin via the lung. Diabetes Obes Metab 2005, 7 (Suppl. 1): S5-8.
142. Laube, B.L. Treating diabetes with aerosolized insulin. Chest 2001, 120 (3 Suppl.): 99S-106.
143. Pfizer, Inc. Exubera® - U.S. package insert. January 2006 (information available online at: http://www.accessdata.fda.gov/scripts/cder/dr ugsatfda).
144. Barnett, A.M. Exubera® inhaled insulin: A review. Int J Clin Pract 2004, 58: 394-401.
145. Rave, K., Bott, S., Heinemann, L. et al. Time-action profile of inhaled insulin in comparison with subcutaneously injected insulin lispro and regular human insulin. Diabetes Care 2005, 28: 1077-82.
146. Sha, S., Becker, R.H.A., Willavise, S.A. et al. The effect of smoking cessassion on the absorption of inhaled insulin (Exhubera®). Diabetes 2002, 51 (Suppl. 1): A133.
147. Gelfand, R.A., Schwartz, S., Horton, M. et al. Pharmacological reproducibility of inhaled human insulin pre-meal dosing in patients with type 2 diabetes mellitus (NIDDM). Diabetes 1998, 47 (Suppl. 1): A99.
148. Skyler, J.S., Cefalu, W.T., Kourides, I.A. et al. Efficacy of inhaled human insulin in type 1 diabetes mellitus: A randomised proof-of-concept study. Lancet 2001, 357: 331-5.
149. Quattrin, T., Belanger, A., Bohannon, N.J., Schwartz, S.L.; Exubera Phase III Study Group. Efficacy and safety of inhaled insulin (Exubera®) compared with subcutaneous insulin therapy in patients with type 1 diabetes: Results of a 6-month, randomized, comparative trial. Diabetes Care 2004, 27: 2622-7.
150. Skyler, J.S., Weinstock, R.S., Raskin, P.; Inhaled Insulin Phase III Type 1 Diabetes Study Group. Use of inhaled insulin in a basal/bolus insulin regimen in type 1 diabetic subjects: A 6-month, randomized, comparative trial. Diabetes Care 2005, 28: 1630-5.
151. DeFronzo, R.A., Bergenstal, R.M., Cefalu, W.T. et al.; Exubera Phase III Study Group. Efficacy of inhaled insulin in patients with type 2 diabetes not controlled with diet and exercise: A 12-week, randomized, comparative trial. Diabetes Care 1205, 28: 1922-8.
152. Rosenstock, J., Zinman, B., Murphy, L.J. et al. Inhaled insulin improves glycemic control when substituted for or added to oral combination therapy in type 2 diabetes: A randomized, controlled trial. Ann Intern Med 2005, 143: 549-58.
153. Hollander, P.A., Blonde, L., Rowe, R. et al. Efficacy and safety of inhaled insulin (Exubera®) compared with subcutaneous insulin therapy in patients with type 2 diabetes: Results of a 6-month, randomized, comparative trial. Diabetes Care 2004, 27: 2356-62.
154. Heise, T., Bott, S., Tusek, C. et al. The effect of insulin antibodies on the metabolic action of inhaled and subcutaneous insulin: A prospective randomized pharmacodynamic study. Diabetes Care 2005, 28: 2161-9.
155. Fineberg, S.E., Kawabata, T., Finco-Kent, D., Liu, C., Krasner, A. Antibody response to inhaled insulin in patients with type 1 or type 2 diabetes. An analysis of initial phase II and III inhaled insulin (Exubera®) trials and a two-year extension trial. J Clin Endocrinol Metab 2005, 90: 3287-94.
156. Rosenstock, J., Cappelleri, J.C., Bolinder, B., Gerber, R.A. Patient satisfaction and glycemic control after 1 year with inhaled insulin (Exubera®) in patients with type 1 or type 2 diabetes. Diabetes Care 2004, 27: 1318-23.
157. Freemantle, N., Blonde, L., Duhot, D. et al. Availability of inhaled insulin promotes greater perceived acceptance of insulin therapy in patients with type 2 diabetes. Diabetes Care 2005, 28: 427-8.
158. Schuster, J., Rubsamen, R., Lloyd, P., Lloyd, J. The AERx® aerosol delivery system. Pharm Res 1997, 14: 354-7.
159. Farr, S.J., McElduff, A., Mather, L.E. et al. Pulmonary insulin administration using the AERx® system: Physiological and physicochemical factors influencing insulin effectiveness in healthy fasting subjects. Diabetes Technol Ther 2000, 2: 185-97.
160. Brunner, G.A., Balent, B., Ellmerer, M. et al. Dose-response relation of liquid aerosol inhaled insulin in type 1 diabetic patients. Diabetologia 2001, 44: 305-8.
161. An, B., Reinhardt, R.R. Effects of different durations of breath holding after inhalation of insulin using the AERx® insulin diabetes management system. Clin Ther 2003, 25: 2233-44.
162. Henry, R.R., Mudaliar, S., Chu, N. et al. Young and elderly type 2 diabetic patients inhaling insulin with the AERx® insulin diabetes management system: A pharmacokinetic and pharmacodynamic comparison. J Clin Pharmacol 2003, 43: 1228-34.
163. McElduff, A., Mather, L.E., Kam, P.C., Clauson, P. Influence of acute upper-respiratory tract infection on the absorption of inhaled insulin using the AERx® insulin diabetes management system. Br J Clin Pharmacol 2005, 59: 546-51.
164. Himmelmann, A., Jendle, J., Meilen, A., Petersen, A.H., Dahl, U.L., Wollmer, P. The impact of smoking on inhaled insulin. Diabetes Care 2003, 26: 677-82.
165. Henry, R.R., Mudaliar, S.R., Howland, W.C. 3rd et al. Inhaled insulin using the AERx® insulin diabetes management system in healthy and asthmatic subjects. Diabetes Care 2003, 26: 764-9.
166. Kapitza, C., Hompesch, M., Scharling, B., Heise, T. Intrasubject variability of inhaled insulin in type 1 diabetes: A comparison with subcutaneous insulin. Diabetes Technol Ther 2004, 6: 466-72.
167. Hermansen, K., Ronnemaa, T., Petersen, A.H., Bellaire, S., Adamson, U. Intensive therapy with inhaled insulin via the AERx® insulin diabetes management system: A 12-week proof-of-concept trial in patients with type 2 diabetes. Diabetes Care 2004, 27: 162-7.
168. Cramer, J.A., Okikawa, J., Bellaire, S., Clauson, P. Compliance with inhaled insulin treatment using the AERx® iDMS insulin diabetes management system. Diabetes Technol Ther 2004, 6: 800-7.
169. Rave, K.M., Nosek, L., De La Pena, A. et al. Dose response of inhaled dry-powder insulin and dose equivalence to subcutaneous insulin lispro. Diabetes Care 2005, 28: 2400-5.
170. Garg, S., Rosenstock, J., Muchmore, D., De La Pena, A., Sun, B., Silverman, B. Safety and efficacy of preprandial human insulin inhalation powder (HIIP) delivered by the Lilly/ Alkermes inhaled system versus injectable insulin in patients with type 1 diabetes. Diabetes 2005, 54 (Suppl.): A361.
171. Perera, A.D., Kapitza, C., Nosek, L. et al. Absorption and metabolic effect of inhaled insulin: Intrapatient variability after inhalation via the Aerodose® insulin inhaler in patients with type 2 diabetes. Diabetes Care 2002, 25: 2276-81.
172. Kim, D., Mudaliar, S., Chinnapongse, S. et al. Dose-response relationships of inhaled insulin delivered via the Aerodose® insulin inhaler and subcutaneously injected insulin in patients with type 2 diabetes. Diabetes Care 2003, 26: 2842-7.
173. Kapitza, C., Heise, T., Fishman, R.S. et al. Impact of particle size and aerosolization time on the metabolic effect of an inhaled insulin aerosol. Diabetes Technol Ther 2004, 6: 119-27.
174. Steiner, S., Pfutzner, A., Wilson, B.R., Harzer, O., Heinemann, L., Rave, K. Technosphere™/ Insulin - Proof of concept study with a new insulin formulation for pulmonary delivery. Exp Clin Endocrinol Diabetes 2002, 110: 17-21.
175. Pfutzner, A., Mann, A.E., Steiner, S.S. Technosphere™/Insulin-A new approach for effective delivery of human insulin via the pulmonary route. Diabetes Technol Ther 2002, 4: 589-94.
176. Rave, K., Nosek, L., Heinemann, L. et al. Inhaled micronized crystalline human insulin using a dry powder inhaler: Dose-response and time-action profiles. Diabet Med 2004, 21: 763-8.