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Nguyen, H.N. et al.

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

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 (123)I-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 (123)I-exendin-4 propagated from the esophagus, stomach, and small intestine and then was absorbed into the systemic circulation; with time progressing, (123)I-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.[1]

References

The glucose-lowering potential of exendin-4 orally delivered via a pH-sensitive nanoparticle vehicle and effects on subsequent insulin secretion in vivo. Nguyen, H.N., Wey, S.P., Juang, J.H., Sonaje, K., Ho, Y.C., Chuang, E.Y., Hsu, C.W., Yen, T.C., Lin, K.J., Sung, H.W. Biomaterials (2011) [Pubmed]

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