title: Noninvasive imaging oral absorption of insulin delivered by nanoparticles and its stimulated glucose utilization in controlling postprandial hyperglycemia during OGTT in diabetic rats.
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.
authors.affiliation: Department of Chemical Engineering/Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors.forename: Er-Yuan
authors.initials: EY
authors.lastname: Chuang
authors.forename: Kun-Ju
authors.initials: KJ
authors.lastname: Lin
authors.forename: Fang-Yi
authors.initials: FY
authors.lastname: Su
authors.forename: Fwu-Long
authors.initials: FL
authors.lastname: Mi
authors.forename: Barnali
authors.initials: B
authors.lastname: Maiti
authors.forename: Chiung-Tong
authors.initials: CT
authors.lastname: Chen
authors.forename: Shiaw-Pyng
authors.initials: SP
authors.lastname: Wey
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.forename: Jyuhn-Huarng
authors.initials: JH
authors.lastname: Juang
authors.forename: Hsing-Wen
authors.initials: HW
authors.lastname: Sung
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D004533:Egtazic Acid / Q000737:chemistry; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006863:Hydrogen-Ion Concentration; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D004533:Egtazic Acid; D005947:Glucose
keywords: Chitosan-γPGA–EGTA nanoparticles; Diabetes mellitus; Glucose utilization; Oral insulin absorption; Postprandial hyperglycemia