The glucose-lowering potential of exendin-4 orally delivered via a pH-sensitive nanoparticle vehicle and effects on subsequent insulin secretion in vivo

Ho Ngoc Nguyen, Shiaw Pyng Wey, Jyuhn Huarng Juang, Kiran Sonaje, Yi Cheng Ho, Er-Tuan Chuang, Chia Wei Hsu, Tzu Chen Yen, Kun Ju Lin, Hsing Wen Sung

研究成果: 雜誌貢獻 › 文章

74 引文 (Scopus)

摘要

Exendin-4 is a potent insulinotropic agent in diabetes patients; however, its therapeutic utility is limited due to the frequent injections required. In this study, an orally available exendin-4 formulation, using an enteric-coated capsule containing pH-responsive NPs, was developed. Following oral administration of 123I-labeled-exendin-4 loaded NPs in rats, the biodistribution of the administered drug was investigated using a dual isotope dynamic SPECT/CT scanner. The results showed that the radioactivity of 123I-exendin-4 propagated from the esophagus, stomach, and small intestine and then was absorbed into the systemic circulation; with time progressing, 123I-exendin-4 was metabolized and excreted into the urinary bladder. In the in vivo dissolution study, it was found that the enteric-coated capsule remained intact while in the stomach; the capsule was completely dissolved in the proximal segment of the small intestine and the loaded contents were then released. Oral administration of the capsule containing exendin-4 loaded NPs showed a maximum plasma concentration at 5 h after treatment; the bioavailability, relative to its subcutaneous counterpart, was found to be 14.0 ± 1.8%. The absorbed exendin-4 could then stimulate the insulin secretion and provide a prolonged glucose-lowering effect. The aforementioned results suggest that the orally available exendin-4 formulation developed warrants further exploration as a potential therapy for diabetic patients.
原文英語
頁（從 - 到）2673-2682
頁數10
期刊Biomaterials
卷32
發行號10
DOIs
出版狀態已發佈 - 四月 2011
對外發佈Yes

指紋

Insulin
Nanoparticles
Glucose
Radioactivity
Medical problems
Isotopes
Capsules
Rats
Dissolution
Plasmas
Small Intestine
Oral Administration
Stomach
exenatide
Biological Availability
Esophagus
Urinary Bladder
Therapeutics
Injections
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

引用此文

The glucose-lowering potential of exendin-4 orally delivered via a pH-sensitive nanoparticle vehicle and effects on subsequent insulin secretion in vivo. / Nguyen, Ho Ngoc; Wey, Shiaw Pyng; Juang, Jyuhn Huarng; Sonaje, Kiran; Ho, Yi Cheng; Chuang, Er-Tuan; Hsu, Chia Wei; Yen, Tzu Chen; Lin, Kun Ju; Sung, Hsing Wen.

於: Biomaterials, 卷 32, 編號 10, 04.2011, p. 2673-2682.

研究成果: 雜誌貢獻 › 文章

Nguyen, HN, Wey, SP, Juang, JH, Sonaje, K, Ho, YC, Chuang, E-T, Hsu, CW, Yen, TC, Lin, KJ & Sung, HW 2011, 'The glucose-lowering potential of exendin-4 orally delivered via a pH-sensitive nanoparticle vehicle and effects on subsequent insulin secretion in vivo', Biomaterials, 卷 32, 編號 10, 頁 2673-2682. https://doi.org/10.1016/j.biomaterials.2010.12.044
Nguyen HN, Wey SP, Juang JH, Sonaje K, Ho YC, Chuang E-T 等. The glucose-lowering potential of exendin-4 orally delivered via a pH-sensitive nanoparticle vehicle and effects on subsequent insulin secretion in vivo. Biomaterials. 2011 4月;32(10):2673-2682. https://doi.org/10.1016/j.biomaterials.2010.12.044
Nguyen, Ho Ngoc ; Wey, Shiaw Pyng ; Juang, Jyuhn Huarng ; Sonaje, Kiran ; Ho, Yi Cheng ; Chuang, Er-Tuan ; Hsu, Chia Wei ; Yen, Tzu Chen ; Lin, Kun Ju ; Sung, Hsing Wen. / The glucose-lowering potential of exendin-4 orally delivered via a pH-sensitive nanoparticle vehicle and effects on subsequent insulin secretion in vivo. 於: Biomaterials. 2011 ; 卷 32, 編號 10. 頁 2673-2682.
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abstract = "Exendin-4 is a potent insulinotropic agent in diabetes patients; however, its therapeutic utility is limited due to the frequent injections required. In this study, an orally available exendin-4 formulation, using an enteric-coated capsule containing pH-responsive NPs, was developed. Following oral administration of 123I-labeled-exendin-4 loaded NPs in rats, the biodistribution of the administered drug was investigated using a dual isotope dynamic SPECT/CT scanner. The results showed that the radioactivity of 123I-exendin-4 propagated from the esophagus, stomach, and small intestine and then was absorbed into the systemic circulation; with time progressing, 123I-exendin-4 was metabolized and excreted into the urinary bladder. In the in vivo dissolution study, it was found that the enteric-coated capsule remained intact while in the stomach; the capsule was completely dissolved in the proximal segment of the small intestine and the loaded contents were then released. Oral administration of the capsule containing exendin-4 loaded NPs showed a maximum plasma concentration at 5 h after treatment; the bioavailability, relative to its subcutaneous counterpart, was found to be 14.0 ± 1.8{\%}. The absorbed exendin-4 could then stimulate the insulin secretion and provide a prolonged glucose-lowering effect. The aforementioned results suggest that the orally available exendin-4 formulation developed warrants further exploration as a potential therapy for diabetic patients.",
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AU - Sonaje, Kiran

AU - Ho, Yi Cheng

AU - Chuang, Er-Tuan

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