Oral delivery of insulin associated to polymeric nanoparticles in diabetic rats.
Nanoparticles prepared with a blend of a biodegradable polyester (poly(-epsilon-caprolactone)) and a polycationic non-biodegradable acrylic polymer (Eudragit RS) have been used as a drug carrier for oral administration of insulin. The rate of encapsulation of insulin was around 96%. The therapeutic efficiency of oral insulin nanoparticles (25, 50 and 100 IU/kg) in diabetic rats and the intestinal uptake of fluorescein isothiocyanate (FITC) labelled insulin were studied. When administered orally by force-feeding to diabetic rats, insulin nanoparticles decreased fasted glycemia in a dose dependant manner with a maximal effect observed with 100 IU/kg. These insulin nanoparticles also increased serum insulin levels and improved the glycemic response to an oral glucose challenge for a prolonged period of time. FITC-Insulin-loaded nanoparticles strongly adhered to the intestinal mucosa and labeled insulin, either released and/or still inside nanoparticles, was mainly taken up by the Peyer's patches. It is concluded that polymeric nanoparticles allows the preservation of insulin's biological activity. In addition, the antidiabetic effect can be explained by the mucoadhesive properties of the polycationic polymer (Eudragit) RS) allowing the intestinal uptake of insulin.
Damgé
Christiane
C
INSERM U734-EA 3452, Laboratory of Pharmaceutical Technology, School of Pharmacy, 5 rue Albert Lebrun, BP 80403, 54001 Nancy Cedex, France.
Maincent
Philippe
P
Ubrich
Nathalie
N
D000180:Acrylic Resins / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D053769:Nanocapsules / Q000737:chemistry*; D010316:Particle Size; D010581:Peyer's Patches / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
D000180:Acrylic Resins; D001786:Blood Glucose; D007328:Insulin; D053769:Nanocapsules; D011091:Polyesters; D011108:Polymers; C016240:polycaprolactone; C050528:Eudragit RS