Oral delivery of insulin loaded poly(fumaric-co-sebacic) anhydride microspheres

The bioadhesive polymer, poly(fumaric-co-sebacic) anhydride, p(FASA), was used to fabricate small diameter insulin microspheres and evaluate their in vivo performance in a type I diabetic rat as well as a type I diabetic dog model. The process of phase inversion nanoencapsulation was used to fabricate p(FASA) microspheres containing insulin. Using laser diffraction spectrometry, 90% of the microspheres used in the fed double dose rat experiments were found to have a volumetric diameter of 5.9 mu m or smaller. In comparison, 90% of the microspheres used in fed single dose rat experiments were found to have a volumetric diameter of 2.6 mu m or smaller while the microspheres used in the diabetic dog experiments were found to have a volumetric diameter of 1.2 mu m or smaller. Insulin microspheres administered to diabetic rats in the fed double dose experiment produced a relative bioavailability (RB) of 23.3% while insulin microspheres administered to diabetic rats in the fed single dose experiment produced a RB of 5.5 +/- 1.7%. Insulin microspheres administered to fasted diabetic dogs produced a RB of 5.5 +/- 3.4%. (C) 2007 Elsevier B.V. All rights reserved.