1. Noninvasive imaging oral absorption of insulin delivered by nanoparticles and its stimulated glucose utilization in controlling postprandial hyperglycemia during OGTT in diabetic rats.
- Author
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Chuang EY, Lin KJ, Su FY, Mi FL, Maiti B, Chen CT, Wey SP, Yen TC, Juang JH, and Sung HW
- Subjects
- Administration, Oral, Animals, Diabetes Mellitus, Experimental complications, Diabetes Mellitus, Experimental metabolism, Egtazic Acid chemistry, Female, Fluorescence Resonance Energy Transfer, Glucose metabolism, Glucose Tolerance Test, Hydrogen-Ion Concentration, Hyperglycemia complications, Hyperglycemia metabolism, Hypoglycemic Agents therapeutic use, Insulin therapeutic use, Male, Polyglutamic Acid analogs & derivatives, Polyglutamic Acid chemistry, Rats, Rats, Wistar, Diabetes Mellitus, Experimental drug therapy, Hyperglycemia drug therapy, Hypoglycemic Agents administration & dosage, Hypoglycemic Agents pharmacokinetics, Insulin administration & dosage, Insulin pharmacokinetics, Nanoparticles chemistry
- Abstract
This work examined the feasibility of preparing a pH-responsive nanoparticle (NP) system composed of chitosan and poly(γ-glutamic acid) conjugated with ethylene glycol tetraacetic acid (γPGA-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 Förster resonance energy transfer (FRET), this work also demonstrated the ability of γPGA-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., (Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2013
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