Pharmacodynamics and Pharmacokinetics of Exendin-4 Orally Delivered via an Enteric Coated Capsule Containing Nanoparticle in Diabetic Rats

摘要

An orally available exendin-4 formulation, using an enteric-coated capsule containing pH-sensitive NPs, was studied. 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.