A review of the efficacy and safety of nanoparticle-based oral insulin delivery systems

Abstract

Card JW, Magnuson BA. A review of the efficacy and safety of nanoparticle-based oral insulin delivery systems. Am J Physiol Gastrointest Liver Physiol 301: G956-G967, 2011. First published September 15, 2011 doi:10.1152/ajpgi.00107.2011.-Nanotechnology is providing new and innovative means to detect, diagnose, and treat disease. In this regard, numerous nanoparticle-based approaches have been taken in an effort to develop an effective oral insulin therapy for the treatment of diabetes. This review summarizes efficacy data from studies that have evaluated oral insulin therapies in experimental models. Also provided here is an overview of the limited safety data that have been reported in these studies. To date, the most promising approaches for nanoparticle-based oral insulin therapy appear to involve the incorporation of insulin into complex multilayered nanoparticles that are mucoadhesive, biodegradable, biocompatible, and acid protected and into nanoparticles that are designed to take advantage of the vitamin B 12 uptake pathway. It is anticipated that the continued investigation and optimization of nanoparticle-based formulations for oral delivery of insulin will lead to a much sought-after noninvasive treatment for diabetes. Such investigations also may provide insight into the use of nanoparticle-based formulations for peptide-and protein-based oral treatment of other diseases and for various foodrelated purposes. nanomaterials; nanotechnology; diabetes DIABETES IS A CHRONIC CONDITION in which the pancreas does not produce enough insulin (Type 1 diabetes) or the body is unable to properly utilize insulin (Type 2 diabetes). It is estimated that the worldwide prevalence of diabetes in adults (20 to 79 yr of age) was 6.6% (285 million people) in 2010 and will increase to 7.8% (438 million people) by the year 2030 (23). Subcutaneous (SC) insulin therapy is a common mode of diabetes treatment but can be burdened by complications (hypoglycemia, edema) and low patient compliance (32). As such, considerable effort has been put forth to develop oral insulin formulations that can provide bioactive insulin in a noninvasive manner that poses minimal patient risk.There are numerous barriers to the oral administration of insulin, including the physical barrier, the enzymatic barrier, and the instability of insulin in the gastrointestinal tract (16, 50). The physical barrier refers to the mucus and viscous fluid (containing mucins, enzymes, electrolytes, and water) that line the epithelium of the small intestine, as well as the physical integrity of the intestinal epithelium attributable to tight junctions between cells. The enzymatic barrier refers to the presence of enzymes in the stomach (pepsin) and duodenum (trypsin, chymotrypsin, and carboxypeptidases) that act to break down proteins and peptides including insulin. The stability of insulin in the gastrointestinal tract is low because of large variations in pH during transit and degradation attributable to enzymatic activity. Combined, these factors contribute to a ...

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“…Insulin conjugated to dextran-vitamin B 12 NPs to diabetic rats that had the least amount of cross linking were found to be most effective at lowering blood glucose levels (70-75%) in STZ induced diabetic rats. In addition the hypoglycemic effect lasted for 54 h. This modification showed the greatest hypoglycemic effect with a pharmacological availability of 29.4% (Table 1) [49,52,53].…”

“…The pharmacological availability was 3.02% and 8.47%, respectively, for the chitosan and the modified NPs. In comparison to oral insulin solution the hypoglycaemic effect was increased by 2.8 and 9.8-folds for the chitosan and the modified NPs, respectively [49,50,51].…”

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“…The diabetes mellitus is a socially significant disease which affects many people and will increase to 438 million worldwide by the year 2030, according to the World Health Organization (WHO) [19,20]. Insulin therapy is the best choice for the clinical management of type I diabetes mellitus but its subcutaneous administration leads to a poor patient compliance.…”

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“…The formulation, produced by Biocon, is a fast-acting insulin analogue that reaches maximum blood concentration after 20 minutes with the peak of action noted after 40 minutes. Absorption and action of the preparation is directly proportional to the dose administered [34].…”

“…Maksymalne stężenie leku we krwi obserwowano po 20, a szczyt działania po 40 minutach. Wchłanianie i działanie leku jest wprost proporcjonalne do zastosowanej dawki [34].…”