Novel Approaches for Oral Delivery of Insulin and Current Status of Oral Insulin Products
DOI:
https://doi.org/10.37285/ijpsn.2010.3.3.3Abstract
Diabetes mellitus is a serious pathologic condition that is responsible for major healthcare problems worldwide and costing billions of dollars annually. Insulin replacement therapy has been used in the clinical management of diabetes mellitus for more than 84 years. The present mode of insulin administration is by the subcutaneous route through which insulin is presented to the body in a non-physiological manner having many challenges. Hence novel approaches for insulin delivery are being explored. Challenges to oral route of insulin administration are: rapid enzymatic degradation in the stomach, inactivation and digestion by proteolytic enzymes in the intestinal lumen and poor permeability across intestinal epithelium because of its high molecular weight and lack of lipophilicity. Liposomes, microemulsions, nanocubicles, and so forth have been prepared for the oral delivery of insulin. Chitosan-coated microparticles protected insulin from the gastric environment of the body and released intestinal pH. Limitations to the delivery of insulin have not resulted in fruitful results to date and there is still a need to prepare newer delivery systems, which can produce dose-dependent and reproducible effects, in addition to increased bioavailability.
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Insulin, Oral delivery, Challenges, Approaches, Market status
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Agarwal V, Khan MA. Current status of the oral delivery of insulin. Pharm. Tech. 25(10), 76-90 (2001).
Agarwal V, Reddy IK, Khan MA. Polyethylacrylate-based microparticulate of insulin for oral delivery: preparation and in vitro dissolution stability in the presence of enzyme inhibitors. Int. J Pharm.; 225 (1–2), 31–39 (2001).
Ahmed I, Goldstein B. Diabetes Mellitus, Clin. Dermatol. 24 (4), 237–246 (2006).
Al-Achi A, Greenwood R. Erythrocytes as Oral Delivery Systems for Human Insulin. Drug Dev. Ind. Pharm. 24 (1), 67–72 (1998).
American Diabetes Association Report of the Expert Committee on the Diagnosis of Diabetes Mellitus. Diabetes Care. 20, 1183–1197 (1997).
Cefalu WT. Evolving Strategies for Insulin Delivery and Therapy, Drugs 64 (11), 1149–1161 (2004).
Chang LL, Stout LE, Wong WD. Immunohistochemical localization of insulin degrading enzyme along the rat intestine, in the human colon adenocarcinoma cell line (Caco-2) and in human ileum. J. Pharm. Sci. 86:116-119 (1999).
Cho YW, Flynn M. Oral delivery of insulin. Lancet; 1518-1519 (1989).
Choudhari KB, Labhasetwar V. Liposomes as a Carrier for Oral Administration of Insulin: Effect of Formulation Factors. J. Microencapsul. 11 (3), 319–325 (1994).
Chung H, Kim J, Um JY, Kwon IC, Jeong SY. Self-Assembled Nanocubicle as a Carrier for Peroral Insulin Delivery. Diabetologia 45 (3), 448–451 (2004).
Damge C, Vranckx H, Balschmidt P, Couvreur P. Poly (alkyl cyanoacrylate) Nanospheres for Oral Adminiatration of Insulin. J Pharm Sci. 86 1403–1409 (1997).
Eaimtrakarn S, Ramaprasad YV, Ohno T, Konishi T, Yoshikawa Y, Shibata N. Absorption-enhancing effect of labrasol on the intestinal absorption of insulin in rats. J. Drug Target. 10 (3), 255–260 (2002).
Fujii S, Yokoyama T, Ikegaya K, Sato F, Yokoo N. Promoting effect of the new chymotrypsin inhibitor fk-448 on the intestinal absorption of insulin in rats and dogs. J. Pharm. Pharmacol. 37 (8), 545–549 (1985).
Giriraj KG, Giriraj KT. Oral Insulin-Fact or Fiction. Resonance 38–43 (2003).
Gowthamarajan K, Kulkarni GT. Oral Insulin – Fact or Fiction? Possibilities of achieving oral delivery for insulin. Resonance, 38-46 (2003).
Haak T. "New Developments in the Treatment of Type 1 Diabetes Mellitus" Exp. Clin. Endocronol. Diabetes 107 (3), S108–113 (1999).
Jain D, Panda AK, Majumdar DK. Eudragit S100 entrapped insulin microspheres for oral delivery. AAPS PharmSciTech, 6 (1), 1-27 (2005).
Kim BY, Jeong JH, Park K, Kim JD. Bioadhesive Interaction and Hypoglycemic Effect of Insulin-Loaded Lectin-Microparticle Conjugates in Oral Insulin Delivery System, J. Control. Release 102 (3), 525–38 (2005).
Kooshapur H, Chaideh M. Intestinal transport of human insulin in rat. Med. J. Islamic Academy of Sciences; 12:1, 5-11 (1999).
Korytkowski M. When oral agents fail: practical barriers to starting insulin. Int. J. Obesity 26(3), S18 – S24 (2002).
Krauland AH, Guggi D, Bernkop-Schnurch A. Oral Insulin Delivery: The Potential of Thiolated Chitosan-Insulin Tablets on Nondiabetic Rats. J Control Release 95 (3), 547–55 (2004).
Kumar A, Lahiri SS, Singh H. Development of PEGDMA: MAA based hydrogel Microparticles for oral insulin delivery. Int. J. Pharm. 12: 323(1-2):117-24 (2006).
Lee VH. Oral route of peptide and protein drug delivery In Peptide
and Protein Drug Delivery, Chapter 16, Marcel Dekker Inc., New York, 1991, 691–738
Li CL, Deng YJ. Oil-based formulations for oral delivery of insulin. J. Pharm. Pharmacol. 56 (9), 1101–1107 (2004).
Lin YH, Chen CT, Liang HF, Kulkarni AR, Lee PW, Chen CH. Novel nanoparticles for oral insulin delivery via the paracellular pathway. Nanotechnology 18: 105102, 1-10 (2007).
Lin YH, Mi FL, Chen CT, Chang WC, Peng SF, Liang HF. Preparation and characterization of nanoparticles shelled with chitosan for oral insulin delivery. Biomacromolecules 8:146-152 (2007).
Liu H, Tang R, Pan WS, Zhang Y, Liu H. Potential utility of various protease inhibitors for improving the intestinal absorption of insulin in rats. J Pharm Pharmacol. 55(11):1523-9 (2003).
Lowman AM, Morishita M, Kajita M, Nagai T, Peppas NA. Oral Delivery of Insulin Using pH-Responsive Complexation Gels. J. Pharm. Sci. 88 (9): 933-936 (1999).
Morishita M, Goto T, Nakamura K, Lowman AM, Takayama K, Peppas NA. Novel oral insulin delivery systems based on complexation polymer hydrogels: Single and multiple administration studies in type 1 and 2 diabetic rats. J. Cont. Release 110:587-594 (2006).
Morishita M, Peppas NA. Is the oral route possible for peptide and protein drug delivery? Drug Discovery Today 11:19-20 (2006).
Musabayane CT, Munjeri O, Bwititi P, Osim EE. Orally administered, insulin-loaded amidated pectin hydrogel beads sustain plasma concentrations of insulin in streptozotocin-diabetic rats. J. Endocrinology 164:1–6 (2000).
Nakamura K, Murray RJ, Joseph JI, Peppas NA, Morishita M, Lowman AM. Oral insulin delivery using P(MAA-g-EG) hydrogels: Effects of network morphology on insulin delivery characteristics. J. Cont. Release, 95:589-599 (2004).
Pamnani D. Reality Check on Oral Insulin, Pharma Express, 16-31, (2008).
Pan Y, Li YJ, Zhao HY. Bioadhesive polysaccharide in protein delivery system: Chitosan nanoparticles improve the intestinal absorption of insulin in vivo. Int. J. Pharm. 249:139-47 (2002).
Patki VP, Jagasia SH. Progress made in noninvasive insulin delivery. Ind. J. Pharmacol. 28: 143-151 (1996).
Patricia M, Eisinbarth GS. "Pathogenesis: Prediction and Trials for the Prevention of Insulin Dependent (Type 1) Diabetes Mellitus." Adv. Drug Del. Rev. 35: 143–156 (1999).
Pearlman R, Nguyen TH. "Analysis of Protein Drugs," in Peptide and Protein Drug Delivery, V.H.L. Lee, Marcel Dekker, New York, 1991.
Plate NA, Valuev IL, Sytov GA. Mucoadhesive polymers with immobilized proteinase inhibitors for oral administration of protein drugs. Biomaterials; 23 (7), 1673–1677 (2002).
Rang HP, Dale MM, and Ritter JM. Pharmacology, S. Beasley, Laurence Hunter, London, England, 1995.
Rieux A, Fievez V, Garinot M, Schneider YJ, Preat V. Nanoparticles as potential oral delivery systems of proteins and vaccines: A mechanistic approach. J. Cont. Release; 116: 1-27 (2006).
Saffran M, Kumar GS, Savariar C, Burnham JC, Williams F, Neckers DC. A new approach to the oral administration of insulin and other peptide drugs. Science; 233(4768):1081-4 (1986).
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).
Salamat-Miller N, Johnston TP. Current strategies used to enhance the paracellular transport of therapeutic polypeptides across the intestinal epithelium. Int. J. Pharm. 294: 201–216 (2005).
Schilling RJ, Mitra AK. Intestinal mucosal transport of insulin. Int. J. Pharm. 62: 53-64 (1999).
Shah RB, Ahsan F, Khan MA. Oral delivery of proteins: Progress and prognostication. Crit. Rev. Ther. Drug Carrier Syst. 19(2): 135–169 (2002).
Soltero R, Ekwuribe N. The oral delivery of protein and peptide drugs- A report. Innovat. Pharmaceut. Technol. 1:106–110 (2001).
Thanou M, Verhoef JC, Junginger HE. Chitosan and its derivatives as intestinal absorption enhancers. Adv. Drug. Delivery. 50: S91-S101 (2001).
Toorisaka E, Hashida M, Kamiya N, Ono H, Kokazu Y, Goto M. An enteric-coated dry emulsion formulation for oral insulin delivery. J. Cont. Release; 107: 91-96 (2005).
Tozaki H. Chitosan Capsules for Colon-Specific Drug Delivery: Improvement of Insulin Absorption from the Rat Colon. J. Pharm. Sci. 86 (9), 1016–1021 (1997).
Tuesca A, Lowman A. The oral delivery of insulin using protein conjugates in complexation hydrogels. Poster presentation, Biomaterials and Drug Delivery Laboratory, DrexelUniversity, 2006.
Yamamoto A, Taniguchi T, Rikyuu K, Tsuji T, Fujita T, Murakami M, Mranishi S. Effects of various protease inhibitors on the intestinal absorption and degradation of insulin in rats. Pharm. Res. 11 (10), 1496–1500 (1994).
Yeap BB. Primary Care Diabetes: What Options are There? Aust. Fam. Physician. 30 (12), 1122–1128 (2001).
Yupeng R, Seng LT. Oral GIT – Hydrogel system for treating type 1 diabetes – A Report.
Ziv E, Lior O, Kidron M. Absorption of protein via the intestinal walls: A quantitative model. Biochem. Pharmacol. 39 (7), 1035–1039 (1987).
