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 |
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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 - 4月 2011 |
對外發佈 | 是 |
ASJC Scopus subject areas
- 生物材料
- 生物工程
- 陶瓷和複合材料
- 材料力學
- 生物物理學