The effect of site of administration in the gastrointestinal tract on the absorption of insulin from nanocapsules in diabetic rats.
Isobutylcyanoacrylate nanocapsules have been used as drug carriers for the enteral absorption of insulin. Their absorption has been studied by measuring fasted glycaemia in streptozotocin-induced diabetic rats after a single administration of encapsulated insulin (100 units kg-1) at various sites along the gastrointestinal tract. Glycaemia decreased from the second day, the intensity and duration depending on the site of administration (65% ileum, 59% stomach, 52% duodenum and jejunum, 34% colon). This hypoglycaemic effect lasted up to the 18th day after administration for ileum and jejunum, the 15th day for stomach and duodenum, and the 13th day for colon. In-vitro, nanocapsules protect insulin against proteolysis from pepsin, chymotrypsin and trypsin. These results suggest (i) that insulin is protected by nanocapsules in the gastrointestinal tract, (ii) that it is absorbed in an active form, and (iii) that ileum is the most potent site of absorption.
Michel
C
C
INSERM-Unité 61, Biologie Cellulaire et Physiopathologie Digestives, Strasbourg, France.
Aprahamian
M
M
Defontaine
L
L
Couvreur
P
P
Damgé
C
C
D000818:Animals; D002214:Capsules; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004337:Drug Carriers; D004655:Emulsions; D005753:Gastric Mucosa / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002214:Capsules; D004337:Drug Carriers; D004655:Emulsions; D007328:Insulin