Oral Insulin Delivery Systems

The addition of PEG to the gels was critical because the PEG chains participate in the macromolecular complexes, function as a peptide stabilizer and enhance the mucoadhesive characteristics of the gels. In this work, strong dose-dependent hypoglycemic effects were observed in healthy and diabetic rats following oral administration of these gels. 

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Morishita, M., et al. 2006. 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. 

Mundargi, R.C. Rangaswamy, V. Aminabhavi, T.M. pH-Sensitive oral insulin delivery systems using Eudragit microspheres. Drug Dev. Ind. Pharm. 2011, 37 (8), 977-985. 

Kim, B.Y, Jeong, J.H., Park, K., Kim, J.D. Bioadhesive interaction and hypoglycemic effect of insulin-loaded lectin-microparticle conjugates in oral insulin delivery system. J. Contr. Release, 102,525, 2005. 

ACRYLIC-BASED COPOLYMERS FOR ORAL INSULIN DELIVERY SYSTEMS... 

Deutel, B., M. Greindl, et al. (2008). Novel insulin thiomer nanoparticles in vivo evaluation of an oral drug delivery system. Biomacromolecules 9(1) 278-85. 

Li, P., Tan, A., Prestidge, C.A., Nielsen, H.M., Mullertz, A., 2014. Self-nanoemulsifying drug delivery systems for oral insulin delivery in vitro and in vivo evaluations of enteric coating and drug loading. Int. J. Pharm. 477, 390—398. 

In a PEC used to deliver a protein, the latter is often used as one of the polyelectrolyte components of the complex. Examples of PECs in which one of the two polyelectrolyte components is an active substance itself, are complexes of chitosan and insulin. The PEC composed of trimethyl chitosan (TMC) and pegylated TMC (PEG-g-TMC) can be obtained simply by mixing the solutions of TMC and insulin at various mass and charge ratios. These PECs were stable in simulated intestinal fluid at pH 6.8. However, they disintegrated in simulated gastrointestinal fluid at pH 1.2. The PECs also protected insulin from temperature-induced denaturation up to 50 °C and from degradation by trypsin. Based on these results, the authors suggested that polyelectrolyte complexation can be a useful technique for fabrication of insulin delivery systems for oral administration. 

Multiple emulsions have also been proposed for the oral delivery of proteins. Because of the relatively large quantities of insulin historically available and the well-known interest in alternative insulin delivery systems (see Chapter 13), the incorporation of insulin within W/OAV multiple emulsions for oral administration has served as the model system (Engel et al, 1968 Shichiri et al, 1974). Engel et al (1968) reported on the in-traduodenal administration of insulin multiple emulsions to Wistar rats... 

Virtually all therapeutic proteins must enter the blood in order to promote a therapeutic effect. Such products must usually be administered parenterally. However, research continues on the development of non-parenteral routes which may prove more convenient, less costly and obtain improved patient compliance. Alternative potential delivery routes include transdermal, nasal, oral and bucal approaches, although most progress to date has been recorded with pulmonary-based delivery systems (Chapter 4). An inhaled insulin product ( Exubera , Chapters 4 and 11) was approved in 2006 for the treatment of type I and II diabetes. 

Morcol, T., et al. 2004. Calcium phosphate-PEG-insulin-casein (CAPIC) particles as oral delivery systems for insulin. Int J Pharm 277 91. 

Al-Achi, A., and R. Greenwood. 1998. Erythrocytes as oral delivery systems for human insulin. Drug Dev Ind Pharm 24 67. 

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