8 results on '"Chen, Chiung-Tong"'
Search Results
2. 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
- Full Text
- View/download PDF
3. Combination therapy via oral co-administration of insulin- and exendin-4-loaded nanoparticles to treat type 2 diabetic rats undergoing OGTT.
- Author
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Chuang EY, Nguyen GT, Su FY, Lin KJ, Chen CT, Mi FL, Yen TC, Juang JH, and Sung HW
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- Administration, Oral, Animals, Cattle, Chitosan chemistry, Drug Combinations, Drug Delivery Systems, Exenatide, Glucose Tolerance Test, Hypoglycemic Agents pharmacokinetics, Insulin pharmacokinetics, Intestinal Absorption, Particle Size, Peptides pharmacokinetics, Polyglutamic Acid analogs & derivatives, Polyglutamic Acid chemistry, Rats, Rats, Wistar, Venoms pharmacokinetics, Diabetes Mellitus, Experimental drug therapy, Hypoglycemic Agents administration & dosage, Insulin administration & dosage, Nanoparticles chemistry, Peptides administration & dosage, Venoms administration & dosage
- Abstract
Current insulin therapy via subcutaneous administration can lead to occasional hypoglycemia and peripheral hyperinsulinemia, due to its nonphysiological route. This study evaluates the feasibility of using bovine insulin and exendin-4 in a form of combination therapy, as orally delivered by nanoparticles composed of chitosan and poly(γ-glutamic acid) (CS/γPGA NPs), to control blood glucose levels in rats with type 2 diabetes mellitus (T2DM) undergoing the oral glucose tolerance test. Experimental results indicate that CS/γPGA NPs could enhance the intestinal paracellular permeation; consequently, the exogenous bovine insulin and exendin-4 could be delivered into the liver and pancreas, where they could elicit their glucoregulatory activities. In response to the stimulus of exogenously delivered bovine insulin and the endogenously secreted rat insulin stimulated by the ingested exendin-4, significant glucose utilizations were found in the cardiac and skeletal muscles, resulting in the glucose-lowering effect. Owing to its synergic stimulation effects, the hypoglycemic effect of oral ingestion of NPs containing bovine insulin and exendin-4 was significantly greater than that of the group solely treated with insulin NPs. Above results demonstrate that oral combination therapy with bovine insulin and exendin-4 improves the modulation of blood glucose levels in T2DM rats, making it highly promising for treating those T2DM patients not adequately controlled by the current insulin therapy., (2013 Published by Elsevier Ltd.)
- Published
- 2013
- Full Text
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4. In vivo evaluation of safety and efficacy of self-assembled nanoparticles for oral insulin delivery.
- Author
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Sonaje K, Lin YH, Juang JH, Wey SP, Chen CT, and Sung HW
- Subjects
- Administration, Oral, Animals, Biological Transport, Caco-2 Cells, Drug Evaluation, Humans, Insulin metabolism, Insulin pharmacology, Male, Microscopy, Electron, Transmission, Nanoparticles adverse effects, Nanoparticles ultrastructure, Rats, Rats, Wistar, Insulin administration & dosage, Insulin chemistry, Nanoparticles administration & dosage, Nanoparticles chemistry
- Abstract
A variety of approaches have been studied in the past to overcome the problems encountered with the oral delivery of insulin, but with little success. In this study, self-assembled nanoparticles (NPs) with a pH-sensitive characteristic were prepared by mixing the anionic poly-gamma-glutamic acid solution with the cationic chitosan solution in the presence of MgSO(4) and sodium tripolyphosphate. The in vitro results found that the transport of insulin across Caco-2 cell monolayers by NPs appeared to be pH-dependent; with increasing pH, the amount of insulin transported decreased significantly. An in vivo toxicity study was performed to establish the safety of the prepared NPs after oral administration. Additionally, the impact of orally administered NPs on the pharmacodynamics (PD) and pharmacokinetics (PK) of insulin was evaluated in a diabetic rat model. The in vivo results indicated that the prepared NPs could effectively adhere on the mucosal surface and their constituted components were able to infiltrate into the mucosal cell membrane. The toxicity study indicated that the NPs were well tolerated even at a dose 18 times higher than that used in the PD/PK study. Oral administration of insulin-loaded NPs demonstrated a significant hypoglycemic action for at least 10h in diabetic rats and the corresponding relative bioavailability of insulin was found to be 15.1+/-0.9%. These findings suggest that the NPs prepared in the study are a promising vehicle for oral delivery of insulin.
- Published
- 2009
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5. Oral delivery of peptide drugs using nanoparticles self-assembled by poly(gamma-glutamic acid) and a chitosan derivative functionalized by trimethylation.
- Author
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Mi FL, Wu YY, Lin YH, Sonaje K, Ho YC, Chen CT, Juang JH, and Sung HW
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- Administration, Oral, Animals, Caco-2 Cells, Drug Carriers chemical synthesis, Electric Impedance, Enzyme-Linked Immunosorbent Assay, Epithelial Cells metabolism, Humans, Hydrogen-Ion Concentration, Insulin administration & dosage, Methylation, Models, Molecular, Molecular Conformation, Polyglutamic Acid chemistry, Polymers chemical synthesis, Solubility, Chitosan chemistry, Drug Carriers chemistry, Insulin chemistry, Insulin pharmacology, Nanoparticles chemistry, Polyglutamic Acid analogs & derivatives, Polymers chemistry
- Abstract
In the study, chitosan (CS) was conjugated with trimethyl groups for the synthesis of N-trimethyl chitosan (TMC) polymers with different degrees of quaternization. Nanoparticles (NPs) self-assembled by the synthesized TMC and poly(gamma-glutamic acid) (gamma-PGA, TMC/gamma-PGA NPs) were prepared for oral delivery of insulin. The loading efficiency and loading content of insulin in TMC/gamma-PGA NPs were 73.8 +/- 2.9% and 23.5 +/- 2.1%, respectively. TMC/gamma-PGA NPs had superior stability in a broader pH range to CS/gamma-PGA NPs; the in vitro release profiles of insulin from both test NPs were significantly affected by their stability at distinct pH environments. At pH 7.0, CS/gamma-PGA NPs became disintegrated, resulting in a rapid release of insulin, which failed to provide an adequate retention of loaded insulin, while the cumulative amount of insulin released from TMC/gamma-PGA NPs was significantly reduced. At pH 7.4, TMC/gamma-PGA NPs were significantly swelled and a sustained release profile of insulin was observed. Confocal microscopy confirmed that TMC40/gamma-PGA NPs opened the tight junctions of Caco-2 cells to allow the transport of insulin along the paracellular pathway. Transepithelial-electrical-resistance measurements and transport studies implied that CS/gamma-PGA NPs can be effective as an insulin carrier only in a limited area of the intestinal lumen where the pH values are close to the p K a of CS. In contrast, TMC40/gamma-PGA NPs may be a suitable carrier for transmucosal delivery of insulin within the entire intestinal tract.
- Published
- 2008
- Full Text
- View/download PDF
6. Preparation and characterization of nanoparticles shelled with chitosan for oral insulin delivery.
- Author
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Lin YH, Mi FL, Chen CT, Chang WC, Peng SF, Liang HF, and Sung HW
- Subjects
- Administration, Oral, Animals, Blood Glucose metabolism, Caco-2 Cells, Cell Membrane Permeability, Chitosan pharmacology, Diabetes Mellitus, Experimental drug therapy, Humans, Hydrogen-Ion Concentration, Polyglutamic Acid analogs & derivatives, Polyglutamic Acid chemistry, Rats, X-Ray Diffraction, Chitosan chemistry, Drug Delivery Systems, Insulin administration & dosage, Nanoparticles chemistry
- Abstract
Nanoparticles (NPs) composed of chitosan (CS) and poly(gamma-glutamic acid) (gamma-PGA) were prepared by a simple ionic-gelation method for oral insulin delivery. Fourier transform infrared (FT-IR) spectra indicated that CS and gamma-PGA were ionized at pH 2.5-6.6, while X-ray diffractograms demonstrated that the crystal structure of CS was disrupted after it was combined with gamma-PGA. The diameters of the prepared NPs were in the range of 110-150 nm with a negative or positive surface charge, depending on the relative concentrations of CS to gamma-PGA used. The NPs with a positive surface charge (or shelled with CS) could transiently open the tight junctions between Caco-2 cells and thus increased the paracellular permeability. After loading of insulin, the NPs remained spherical and the insulin release profiles were significantly affected by their stability in distinct pH environments. The in vivo results clearly indicated that the insulin-loaded NPs could effectively reduce the blood glucose level in a diabetic rat model.
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- 2007
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7. Self-assembling bubble carriers for oral protein delivery.
- Author
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Chuang, Er-Yuan, Lin, Kun-Ju, Lin, Po-Yen, Chen, Hsin-Lung, Wey, Shiaw-Pyng, Mi, Fwu-Long, Hsiao, Hsu-Chan, Chen, Chiung-Tong, and Sung, Hsing-Wen
- Subjects
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PROTEIN drugs , *ORAL medication , *MOLECULAR self-assembly , *INSULIN , *HYPOGLYCEMIC agents , *SURFACE active agents - Abstract
Successful oral delivery of therapeutic proteins such as insulin can greatly improve the quality of life of patients. This study develops a bubble carrier system by loading diethylene triamine pentaacetic acid (DTPA) dianhydride, a foaming agent (sodium bicarbonate; SBC), a surfactant (sodium dodecyl sulfate; SDS), and a protein drug (insulin) in an enteric-coated gelatin capsule. Following oral administration to diabetic rats, the intestinal fluid that has passed through the gelatin capsule saturates the mixture; concomitantly, DTPA dianhydride produces an acidic environment, while SBC decomposes to form CO 2 bubbles at acidic pH. The gas bubbles grow among the surfactant molecules (SDS) owing to the expansion of the generated CO 2 . The walls of the CO 2 bubbles consist of a self-assembled film of water that is in nanoscale and may serve as a colloidal carrier to transport insulin and DTPA. The grown gas bubbles continue to expand until they bump into the wall and burst, releasing their transported insulin, DTPA, and SDS into the mucosal layer. The released DTPA and SDS function as protease inhibitors to protect the insulin molecules as well as absorption enhancers to augment their epithelial permeability and eventual absorption into systemic circulation, exerting their hypoglycemic effects. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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8. Effects of chitosan-nanoparticle-mediated tight junction opening on the oral absorption of endotoxins
- Author
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Sonaje, Kiran, Lin, Kun-Ju, Tseng, Michael T., Wey, Shiaw-Pyng, Su, Fang-Yi, Chuang, Er-Yuan, Hsu, Chia-Wei, Chen, Chiung-Tong, and Sung, Hsing-Wen
- Subjects
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CHITOSAN , *NANOPARTICLES , *ABSORPTION (Physiology) , *ENDOTOXINS , *HYDROGEN-ion concentration , *INSULIN , *HYPOGLYCEMIA , *TOMOGRAPHY , *TRANSMISSION electron microscopy - Abstract
Abstract: Recently, we reported a pH-responsive nanoparticle (NP) system shelled with chitosan (CS), which could effectively increase the oral absorption of insulin and produce a hypoglycemic effect, presumably due to the CS-mediated tight junction (TJ) opening. It has been often questioned whether CS can also enhance the absorption of endotoxins present in the small intestine. To address this concern, we studied the effect of CS NPs on the absorption of lipopolysaccharide (LPS), the most commonly found toxin in the gastrointestinal tract. To follow their biodistribution by the single-photon emission computed tomography/computed tomography, LPS and insulin were labeled with 99mTc-pertechnetate (99mTc-LPS) and 123iodine (123I-insulin), respectively. The 99mTc-LPS was ingested 1 h prior to the administration of the 123I-insulin-loaded NPs to mimic the physiological conditions. The confocal and TEM micrographs show that the orally administered CS NPs were able to adhere and infiltrate through the mucus layer, approach the epithelial cells and mediate to open their TJs. The radioactivity associated with LPS was mainly restricted to the gastrointestinal tract, whereas 123I-insulin started to appear in the urinary bladder at 3 h post administration. This observation indicates that the insulin-loaded in CS NPs can traverse across the intestinal epithelium and enter the systemic circulation, whereas LPS was unable to do so, probably because of the charge repulsion between the anionic LPS in the form of micelles and the negatively charged mucus layer. Our in vivo toxicity study further confirms that the enhancement of paracellular permeation by CS NPs did not promote the absorption of LPS. These results suggest that CS NPs can be used as a safe carrier for oral delivery of protein drugs. [Copyright &y& Elsevier]
- Published
- 2011
- Full Text
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