Oral delivery of the amylin receptor agonist pramlintide

Abstract

Amylin receptor agonism safely benefit diabetic patients, reducing the insulin requirements and glycemic excursions. Pramlintide is the triple proline human amylin analogue first used as injectable drug, but lacking physico-chemical compatibility when co-formulated with insulin. Here, we report the design and characterization of polymeric microparticles for oral delivery of pramlintide. Eudragit S100, a gastric-resistant polymer, was used in preparation of pramlintide-loaded spherical microcapsules by double emulsion and solvent evaporation technique, with approximately 66 μm ± 11 particle size, with 83.2% ± 2.7 efficiency for pramlintide entrapment and 67.6% ± 2.1 yield. Intra-venous pramlintide free in solution showed a plasmatic half-life of 6.8 min in mice. In contrast, oral delivery of acid-resistant pramlintide-loaded microparticles in mice showed a protracted release for 120 min compared to 30 min obtained for pramlintide in solution. Our data provide evidences for the potential use of the oral route in the therapeutic development of pramlintide formulations.