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 1 diabetic rat as well as a type 1 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 microm 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 microm or smaller while the microspheres used in the diabetic dog experiments were found to have a volumetric diameter of 1.2 microm 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%.
Furtado
Stacia
S
Brown University, Department of Molecular Pharmacology, Physiology and Biotechnology, Box GB-393, Providence, RI 02912, USA.
Abramson
Danielle
D
Burrill
Roxanne
R
Olivier
Gloria
G
Gourd
Celinda
C
Bubbers
Emily
E
Mathiowitz
Edith
E
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003652:Decanoic Acids / Q000737:chemistry*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy; D004285:Dogs; D005260:Female; D005650:Fumarates / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D007328:Insulin / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D011913:Rats, Inbred BB
D001786:Blood Glucose; D003652:Decanoic Acids; D005650:Fumarates; D007004:Hypoglycemic Agents; D007328:Insulin; D011108:Polymers; C473130:poly(fumaric-co-sebacic acid)