Computing and Library Services - delivering an inspiring information environment

Various non-injectable delivery systems for the treatment of diabetes mellitus

Yadav, N., Morris, Gordon, Harding, S. E., Ang, S. and Adams, G. G. (2009) Various non-injectable delivery systems for the treatment of diabetes mellitus. Endocrine, Metabolic and Immune Disorders - Drug Targets, 9 (1). pp. 9-13. ISSN 1871-5303

Metadata only available from this repository.


Diabetes mellitus (diabetes) is suffered by more than 180 million people and is responsible for approximately 2.9 million deaths each year. This mortality rate is expected to increase by 50 % in the next decade. Due to the inconvenience of the traditional treatment of diabetes by subcutaneous administration of insulin injection, various attempts are made in the production, purification, formulation and methods of delivery of insulin. However, despite advances in recent years, these attempts have met with limited success. Various alternative routes such as rectal, ocular, nasal, pulmonary and oral have been exploited. The pulmonary route offers great potential for the delivery of polypeptide drugs due to the large surface area for insulin absorption in the respiratory tract. But due to its low bioavailability, oral route is intensely investigated for the insulin delivery. Microencapsulation, as one of the delivery systems utilising oral route, has shown some potential progress in insulin delivery; though it is at an early stage yet it has proved to be quite encouraging providing new less toxic immunosuppressive agents. Microencapsulation may prove to be an attractive delivery system for controlled release of insulin and beneficial for therapeutic, bio-efficient and bio-effective drug delivery. In this review we discuss the possible alternative routes for insulin delivery (ocular, nasal, pulmonary and oral) and advantages and disadvantages of each. Furthermore we consider the different drug delivery strategies available (aerosols, dry powder inhalers, synthetic beta cells, hydrogels and microcapsules) and their current and potential applications with respect to the different insulin delivery routes. © 2009 Bentham Science Publishers Ltd.

Item Type: Article
Uncontrolled Keywords: Aerosols Dry powder inhalers Hydrogels Insulin delivery Microcapsules eye drops insulin oral antidiabetic agent recombinant human insulin aerosol arterial pressure cell therapy clinical trial diabetes mellitus diastolic blood pressure drug absorption drug bioavailability drug blood level drug clearance drug delivery system drug dosage form comparison drug formulation drug instillation dry powder human hydrogel hypoglycemia injection site pain insulin dependent diabetes mellitus insulin release insulin treatment microcapsule non insulin dependent diabetes mellitus nonhuman nose irritation pancreas islet beta cell patient compliance powder inhaler review side effect systolic blood pressure nebulizer Capsules Drug Delivery Systems Humans Nebulizers and Vaporizers
Subjects: Q Science > QD Chemistry
Schools: School of Applied Sciences
Related URLs:
References: Language of Original Document: English Correspondence Address: Adams, G.G.; Insulin and Diabetes Experimental Research Group, University of Nottingham, Faculty of Medicine and Health Science, Clifton Boulevard, Nottingham NG7 2RD, United Kingdom; email: Chemicals/CAS: insulin, 9004-10-8; Aerosols; Capsules; Hydrogels; Insulin, 11061-68-0 Tradenames: Aerodose, Aerogen, United States; AERx, Aradigm, United States; AIR, Alkermes, United States; AIR, Lilly, United States; Exebura, Nektar, United States; Technospere, MannKind, United States Manufacturers: Aerogen, United States; Alkermes, United States; Aradigm, United States; Lilly, United States; MannKind, United States; Nektar, United States References: last accessed on 2008-01-28Diabetes Atlas, 3rd ed. © International Diabetes Federation, 2006Williams, R., Airey, M., Baxter, H., Forrester, J., Kennedy-Martin, T., Girach, A., Epidemiology of diabetic retinopathy and macular oedema: A systematic review (2004) Eye, 18 (10), pp. 963-983; Tesch, G.H., Nikolic-Paterson, D.J., Monocyte chemoattractant protein-1 promotes the development of diabetic renal injury in streptozotocin-treated mice (2006) Nephron. Exp. Nephrol, 104 (2), pp. e57-e62; Evans, M.J., Kaufman, M.H., Establishment in culture of pluripotential cells from mouse embryos (1981) Nature, 292 (5819), pp. 154-156; Somers, E.C., Thomas, S.L., Smeeth, L., Hall, A.J., Autoimmune diseases co-occurring within individuals and within families: A systematic review (2004) Epidemiology, 17 (2), pp. 202-217; Steil, G.M., Panteleon, A.E., Rebrin, K., Closed-loop insulin delivery - the path to physiological glucose control (2004) Adv. Drug Deliv. Rev, 56 (2), pp. 125-144; Varshosaz, J., Insulin delivery systems for controlling diabetes (2007) Recent Patents Endocrine, Metab. Immun. Drug Discov, 16 (1), pp. 25-40; Silvaa, C., Ribeirob, A.J., Ferreirac, D., Veigaa, F., Insulin encapsulation in reinforced alginate microspheres prepared by internal gelation (2006) Eur. J. Pharm. Sci, 29 (2), pp. 148-159; Barichello, J.M., Morishita, M., Takayama, K., Chiba, Y., Tokiwa, S., Nagai, T., Enhanced rectal absorption of insulin-loaded Pluronic® F-127 gels containing unsaturated fatty acids (1999) Int. J. Pharm, 183 (2), pp. 125-132; Owens, D.R., Zinman, B., Bolli, G., Alternative routes of insulin delivery (2003) Diabet. Med, 20 (11), pp. 886-898; Narayani, R., Artificial cell therapy: New strategies for the therapeutic delivery of live bacteria (2001) Trends Biomater. Artifi. Organs, 15 (1), pp. 12-16; Lee, Y.C., Simamora, P., Yalkowsky, S.H., Systemic delivery of insulin via an enhancer-free ocular device (1997) J. Pharm. Sci, 86 (12), pp. 1361-1364; Chiou, G.C.Y., Effect of formulation on the systemic absorption of insulin from enhancer-free ocular devices (1991) Annu. Rev. Pharmacol, 31 (1), pp. 457-467; Lee, Y.C., Simamora, P., Yalkowsky, S.H., Effect of Brij-78 on systemic delivery of insulin from an ocular device (1997) J. Pharm. Sci, 86 (4), pp. 430-433; Jabbal-Gill, I., Fisher, A.N., Rappuoli, R., Davis, S.S., Illum, L., Vaccination of rock bream, Oplegnathus fasciatus (Temminck & Schlegel), using a recombinant major capsid protein of fish iridovirus (1998) Vaccine, 16 (20), pp. 2039-2046; Cernea, S., Raz, I., Intranasal insulin: PK profile designed specifically for prandial treatment of Type 2 Diabetes (2006) Drugs Today, 42 (6), pp. 405-424; Gizurarson, S., Bechgaard, E., Intranasal administration of insulin to humans (1991) Diabetes Res. Clin. Pract, 12 (2), pp. 71-84; Turker, S., Onur, E., Ozer, Y., Pharmaceutical significance of chitosan: A review (2004) Pharm. World Sci, 26 (3), pp. 137-142; Drejer, K., Vaag, A., Bech, K., Hansen, P., Sorensen, A.R., Mygind, N., Poly(alkyl cyanoacrylate) nanospheres for oral administration of insulin (1992) Diabet. Med, 9 (4), pp. 335-340; 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 (1993) Diabetes, 42 (11), pp. 1649-1655; Moses, A.C., Gordon, G.S., Carey, M.C., Flier, J.S., Nasal absorption of insulin: Enhancement by hydrophobic bile salts (1983) Diabetes, 32 (11), pp. 1040-1047; Nolte, M.S., Taboga, C., Salamon, E., Moses, A., Longenecker, J., Flier, J., Karam, J.H., Intra-individual variability of the metabolic effect of inhaled insulin together with an absorption enhancer (1990) Hormone Metab. Res, 22 (3), pp. 170-174; Bruce, D.G., Chisholm, D.J., Storlien, L.H., Borkman, M., Kraegen, E.W., Meal-time intranasal insulin delivery in Type 2 diabetes (1991) Diabet. Med, 8 (4), pp. 366-370; Liu, L., Fishman, M.L., Hicks, K.B., Pectin in controlled drug delivery - a review (2007) Cellulose, 14 (1), pp. 15-24; Liu, L., Fishman, M.L., Kost, J., Hicks, K.B., Pectin-based systems for colon-specific drug delivery via oral route (2003) Biomaterials, 24 (19), pp. 3333-3343; 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 euglycaemic clamp technique (2004) Clin. Ther, 26 (12), pp. 2084-2091; Modi, P., Mihic, M., Lewin, A., The evolving role of oral insulin in the treatment of diabetes using a novel RapidMistSystem (2002) Diab. Metab. Res. Rev, 18 (1), pp. S38-S42; Lin, Y.H., Chen, C.H., Liang, H.F., Kulkarni, A.R., Lee, P.W., Chen, C.H., Sung, H.W., Novel nanoparticles for oral insulin delivery via the paracellular pathway (2007) Nanotechnology, 18 (10), pp. 1-11; Carino, G.P., Jacob, J.S., Mathiowitz, E., Nanosphere based oral insulin delivery (2000) J. Control. Rel, 65 (1-2), pp. 261-269; Mesiha, M., Plakogiannis, F., Vejosoth, S., Nanoparticles of quaternized chitosan derivatives as a carrier for colon delivery of insulin: Ex vivo and in vivo studies (1994) Int. J. Pharm, 111 (3), pp. 213-216; Yamamoto, A., Taniguchi, T., Rikyuu, K., Tsuji, T., Fujita, T., Murakami, M., Muranishi, S., Effects of various protease inhibitors on the intestinal absorption and degradation of insulin in rats (1994) Pharm. Res, 11 (10), pp. 1496-1500; Morishita, I., Morishita, M., Takayama, K., Machida, Y., Nagai, T., Enteral insulin delivery by microspheres in 3 different formulations using Eudragit® L100 and S100 (1993) Int. J. Pharm, 91 (1), pp. 29-37; Sarmento, B., Ribeiro, A., Veiga, F., Ferreira, D., Neufeld, R., Oral bioavailability of insulin contained in polysaccharide nanoparticles (2007) Biomacromolecules, 8 (10), pp. 3054-3060; Jain, D., Panda, A.K., Majumdar, D.K., Eudragit S100 entrapped insulin microspheres for oral delivery (2005) AAPS Pharm. Sci. Tech, 6 (1), pp. E100-E107; Gaensslen, M., Ueber Inhalation von Insulin. (1925) Klin. Wochenschr, 4 (2), p. 71; Banting, F.G., Best, C.H., Macleod, J.J.R., The internal secretion of the pancreas (1922) Am. J. Physiol, 59 (1), p. 479; Cernea, S., Kidron, M., Wohlgelernter, J., Modi, P., Raz, I., Dose-response relationship of oral insulin spray in healthy subjects (2005) Diabetes Care, 28 (6), pp. 1353-1357; Mygind, N., Treating Diabetes With Aerosolized Insulin: In Aerosols in medicine (1985) Principles, diagnosis and therapy, pp. 1-20. , Moren, F, Newhouse, M.T. and Dolovich, M. B. Eds, New York, Elsevier Science Publishers; Byron, P.R., Prediction of drug residence times in regions of the human respiratory tract following aerosol inhalation (1986) J. Pharm. Sci, 75 (5), pp. 433-438; Gil, J., Number and distribution of plasmalemmal vesicles in the lung (1983) Fed. Proc, 42 (8), pp. 2414-2418; Jendle, J.H., Karlberg, B.E., Intrapulmonary insulin administration in healthy volunteers (1996) J. Int. Med, 240 (2), pp. 93-98; Galloway, J.A., Spradlin, C.T., Nelson, R.L., Wnetworth, 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 (1981) Diabetes Care, 4 (3), pp. 366-376; Patton, J., Pulmonary delivery of insulin (2006) Curr. Med. Res. Opin, 22 (3), pp. S5-S11; Scheuch, G., Siekmeier, R., Novel approaches to enhance pulmonary delivery of proteins and peptides (2007) J. Physiol. Pharmacol, 58 (5), pp. 615-625; Agu, R.U., Ugwoke, M.I., Armand, M., Kinget, R., Verbeke, N., The lung as a route for systemic delivery of therapeutic proteins and peptides (2001) Respir. Res, 2 (4), pp. 198-209; Niven, R.W., Delivery of biotherapeutics by inhalation aerosol (1995) Crit. Rev. Ther. Drug Carrier Syst, 12 (2-3), pp. 151-231; Deshpande, D., Blanchard, J., Srinivasan, S., Fairbanks, D., Fujimoto, J., Sawa, T., Wiener-Kronish, J., Gonda, I., Aerosolization of lipoplexes using AERx® pulmonary delivery system (2002) AAPS Pharm. Sci, 4 (3), pp. 1-10; Mandal, T.K., Inhaled insulin for diabetes mellitus (2005) Am. J. Health-Syst. Pharm, 62 (13), pp. 1359-1364; Laube, B.L., Treating diabetes with aerosolised insulin (2001) Chest, 120 (3), pp. 99S-106; Crowder, T.M., Louey, M.D., Sethuraman, V.V., Smyth, H.D.C., Hickey, A., An odyssey in inhaler formulations and design (2001) J. Pharm. Tech, 25 (7), pp. 99-113; Laube, B.L., Benedict, W., Dobs, A.S., Time to peak insulin level, relative bioavailability and effect of site of deposition of nebulized insulin in patients with non-insulin-dependent diabetes mellitus (1998) J. Aerosol. Med, 11 (3), pp. 153-173; Elliott, R.B., Edgar, B.W., Pilcher, C.C., Quested, C., McMaster, J., (1987) Aust. Paediatr. J, 23 (5), pp. 293-297; Selam, J.L., Inhaled insulin for the treatment of diabetes: Projects and devices (2003) Exp. Opin. Pharmacol, 4 (8), pp. 1373-1377; Mumenthaler, M., Hsu, C.C., Pearlman, R., Feasibility study on spray-drying protein pharmaceuticals: Recombinant human growth hormone and tissue-type plasminogen activator (1994) Pharm. Res, 11 (1), pp. 12-20; 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 (2001) Curr. Pharm. Des, 7 (14), pp. 1327-1351; Schultz, H., Mechanisms and factors affecting intrapulmonary particle deposition: Implications for efficient inhalation therapies (1998) Pharmaceut. Sci. Technol, 1 (8), pp. 336-344; Farr, S.J., McElduff, A., Mather, L.E., Okikawa, J., Ward, M.E., Gonda, I., Vojtech, L., Rubsamen, R.M., Pulmonary insulin administrationusing the AERx™ system: Physiological and physiochemical factors influencing insulin effectiveness in healthy fasting subjects (2000) Diabetes Technol. Therapeut, 2 (2), pp. 185-197; Brådvik, I., Wollmer, P., Evander, E., Sloth, M., Lárusdóttir, H., Blom-Bülow, B., Jonson, B., One year follow-up of lung clearance of 99mTc-diethylene traimine penta-acetic acid and diseases activity in sarcodisis (2000) Vasculitis Diffuse Lung Dis, 17 (3), pp. 281-287; Wollmer, P., Evander, E., Biphasic pulmonary clearance of 99mTc-DPTA in smokers (1994) Clin. Physiol, 14 (5), pp. 547-559; Minty, B.D., Royston, D., Jones, J.G., Hulands, G.H., The effect of nicotine on pulmonary epithelial permeability in man (1984) Chest, 86 (1), pp. 72-74; Meignan, M., Rosso, J., Leveau, J., Katz, A., Cinotti, L., Madelaine, G., Galle, P., Exercise increases the lung clearance of inhaled technetium-99m DPTA (1986) J. Nucl. Med, 27 (2), pp. 274-280; Schmekel, B., Borgstrom, L., Wollmer, P., Exercise increases the rate of pulmonary absorption of inhaled terbulatie (1992) Chest, 101 (3), pp. 742-745; Fink, J.B., Metered-dose inhalers, dry powder inhalers, and transitions (2000) Resp. Care, 456 (6), pp. 623-635; Kubelka, J., Huang, R., Keiderling, T.A., Solvent effects on ir and vcd spectra of helical peptides: Dft-based static spectral simulations with explicit water (2005) J. Phys. Chem. B, 109 (16), pp. 8231-8243; Laube, B.L., Georgopoulos, A., Adams 3rd, G.K., Preliminary study of the efficacy of insulin aerosol delivered by oral inhalation in diabetic patients (1993) JAMA, 69 (16), pp. 2106-2109; Maa, Y.F., Prestrelski, S.J., Biopharmaceutical powders particle formation and formulation considerations (2000) Curr. Pharm. Biotech, 1 (3), pp. 283-302; Tyagi, P., Insulin delivery systems: Present trends and the future direction (2002) Ind. J. Pharmacol, 34 (6), pp. 379-389; Thompson, P.J., Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (1998) Am. J. Respir. Crit. Care Med, 157 (5), pp. 199-202; Keller, M. and Müller-Walz, R. (2000) Development of dry powder inhalers WO0028979Chougule, M.B., Padhi, B.K., Jinturkar, K.A., Misra, A., Development of dry powder inhalers (2007) Recent Patents Drug Deliv. Formulat, 1 (1), pp. 11-21; Edwards, D.A., Ben-Jerbria, A., Langer, R., Recent advances in pulmonary drug delivery using large, porous inhaled particles (1998) J. Appl. Physiol, 85 (2), pp. 379-385; Rosenstock, J., Mealtime rapid acting inhaled insulin (Exubera®) improves glycaemic control in patients with type 2 diabetes failing combination oral agents: A 3 month randomised comparative trial (2002) Diabetes, 51 (2), pp. A132-A133; Belanger, A., Efficacy and safety of inhaled insulin (Exubera®) compared to sc insulin therapy in patients with type 2 diabetes. Results of a 6 month randomised comparative trial (2002) Diabetologia, 45 (2), pp. A260; Henry, R.R., Mudaliar, S.R., Howland III, W.C., Chu, N., Kim, D., An, B., Reinhardt, R.R., Pulmonary delivery of insulin using the AERx™ insulin diabetes management system in healthy and asthmatic subjects (2003) Diabetes Care, 26 (3), pp. 764-769; Skyler, J.S., Weinstock, R.S., Raskin, P., Yale, J.F., Barrett, E., Gerich, J.E., Gerstein, H.C., Use of inhaled insulin in a basal/bolus insulin regimen in type 1 diabetic subjects A 6-month, randomized, comparative trial (2005) Diabetes Care, 28 (7), pp. 1630-1635; DeFronzo, R.A., Bergenstal, R.M., Cefalu, W.T., Pullman, J., Lerman, S., Bode, B.W., Phillips, L.S., Efficacy of inhaled insulin in patients with type 2 diabetes not controlled with diet and exercise: A 12-week, randomized, comparative trial (2005) Diabetes Care, 28 (8), pp. 1922-1928; Weiss, S.R., Cheng, S.L., Kourides, I.A., Gelfand, R.A., Landschulz, W.H., The Inhaled Insulin Phase II Study Group: Inhaled insulin provides improved glycemic control in patients with type 2 diabetes mellitus inadequately controlled with oral agents: a randomized controlled trial (2003) Arch. Intern. Med, 163 (19), pp. 2277-2282; Cefalu, W.T., Balagtas, C.C., Landshultz, W.H., Gelfand, R.A., Sustained efficacy and pulmonary safety of inhaled insulin during 2 years of outpatient therapy (2000) Diabetologia, 43 (1), pp. A47; Staniforth, J.N. (1995) Development of dry powder inhalers WO9511666Trofast, J. (1998) New formulation for inhalation having a poured bulk density of from 0.28 to 0.38 g/ml, comprising Formoterol WO9831351Edwards, D.A., Caponetti, G.H., Jeffrey, S., Lotan, N., Hanes, J., Ben-Jebria, A., Langer, R.S., Development of dry powder inhalers (2000), US20006399102Edwards, D.A., Caponetti, G.H., Jeffrey, S., Lotan, N., Hanes, J., Ben-Jebria, A., Langer, R.S., Development of dry powder inhalers (2005), US20050244341Hodson, P.D., Smith, D.K., Velasquez, D.J., Wass, A.C.L., Calhoun, C.D., Development of dry powder inhalers (1998), US5740793Jahr, H., Bretzel, B., Insulin-positive cells in vitro generated from rat bone marrow stromal cells (2003) Transplant. Proc, 35 (6), pp. 2140-2141; Ianus, A., Holz, G.G., Theise, N.D., Hussain, M.A., In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion (2003) J. Clin. Invest, 111 (6), pp. 843-850; Newgard, C.B., An artificial beta cell produced by engineering endocrine cells of the At-T-20 ACTH secreting cells (2005), US5427940Laurance, M.E., Knaack, D., Fiore, D.M., Hegre, O.D., Glucose responsive insulin secreting beta-cell lines (1996), US5534404Stock, P.G., Bluestone, J.A., Beta-cell replacement for type I diabetes (2004) Ann. Rev. Med, 55 (1), pp. 133-156; Tanaka, T., Fillmore, D., Sun, S., Nishio, I., Swislow, G., Shah, A., Phase transitions in ionic gels (1980) Phys. Rev. Lett, 45 (20), pp. 1636-1639; Hoffman, J., Plotner, M., Kuc
Depositing User: Gordon Morris
Date Deposited: 19 May 2011 11:52
Last Modified: 28 Aug 2021 11:06


Downloads per month over past year

Repository Staff Only: item control page

View Item View Item

University of Huddersfield, Queensgate, Huddersfield, HD1 3DH Copyright and Disclaimer All rights reserved ©