Oral delivery of the amylin receptor agonist pramlintide

Abstract

AimThe aims of this study were to design and characterize polymeric microparticles for oral delivery of pramlintide, a triple proline human amylin analogue clinically proved efficient in diabetes therapy. MethodsThe microparticles were prepared with gastric-resistant polymer Eudragit S100 by double-emulsion and solvent evaporation technique. The study responses were repeatability, encapsulation efficiency, yield, morphology, particle size, response to acidic and alkaline milieu and pharmacokinetics. ResultsWe obtained spherical microcapsules, with particle size of 66 m {+/-} 11, 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. ConclusionsOral route is an alternative for therapeutic development of pramlintide formulations. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/566408v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@d75002org.highwire.dtl.DTLVardef@1c5e914org.highwire.dtl.DTLVardef@492823org.highwire.dtl.DTLVardef@ea171b_HPS_FORMAT_FIGEXP M_FIG C_FIG