Noninvasive imaging oral absorption of insulin delivered by nanoparticles and its stimulated glucose utilization in controlling postprandial hyperglycemia during OGTT in diabetic rats

This work examined the feasibility of preparing a pH-responsive nanoparticle (NP) system composed of chitosan and poly(gamma-glutamic acid) conjugated with ethylene glycol tetraacetic acid (gamma PGA-EGTA) for oral insulin delivery in diabetic rats during an oral glucose tolerance test (OGTT). OGTT has been used largely as a model to mimic the period that comprises and follows a meal, which is often associated with postprandial hyperglycemia. Based on Forster resonance energy transfer (FRET), this work also demonstrated the ability of gamma PGA-EGTA to protect insulin from an intestinal proteolytic attack in living rats, owing to its ability to deprive the environmental calcium. Additionally, EGTA-conjugated NPs were effective in disrupting the epithelial tight junctions, consequently facilitating the paracellular permeation of insulin throughout the entire small intestine. Moreover, results of positron emission tomography and computer tomography demonstrated the effective absorption of the permeated insulin into the systemic circulation as well as promotion of the glucose utilization in the myocardium, and skeletal muscles of the chest wall, forelimbs and hindlimbs, resulting in a significant glucose-lowering effect. Above results indicate that as-prepared EGTA-conjugated NPs are a promising oral insulin delivery system to control postprandial hyperglycemia and thus may potentially prevent the related diabetic complications. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved.