Design and in vivo evaluation of a patch delivery system for insulin based on thiolated polymers.
OBJECTIVE
The aim of this study was to develop and evaluate a novel three-layered oral delivery system for insulin in vivo.


METHODS
The patch system consisted of a mucoadhesive layer, a water insoluble backing layer made of ethylcellulose and an enteric coating made of Eudragit. Drug release studies were performed in media mimicking stomach and intestinal fluids. For in vivo studies patch systems were administered orally to conscious non-diabetic rats. Orally administered insulin in aqueous solution was used as control. After the oral administration of the patch systems a decrease of glucose and increase of insulin blood levels were measured.


RESULTS
The mucoadhesive layer, exhibiting a diameter of 2.5mm and a weight of 5mg, comprised polycarbophil-cysteine conjugate (49%), bovine insulin (26%), gluthatione (5%) and mannitol (20%). 74.8+/-4.8% of insulin was released from the delivery system over 6h. Six hours after administration of the patch system mean maximum decrease of blood glucose level of 31.6% of the initial value could be observed. Maximum insulin concentration in blood was 11.3+/-6.2ng/ml and was reached 6h after administration. The relative bioavailability of orally administered patch system versus subcutaneous injection was 2.2%.


CONCLUSIONS
The results indicate that the patch system provides enhancement of intestinal absorption and thereby offers a promising strategy for peroral peptide delivery.
Grabovac
Vjera
V
Institute of Pharmacy, University of Innsbruck, Innrain 52, 6020 Innsbruck, Austria.
Föger
Florian
F
Bernkop-Schnürch
Andreas
A
D000180:Acrylic Resins / Q000737:chemistry*; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001786:Blood Glucose / Q000187:drug effects; D002417:Cattle; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D010592:Pharmaceutic Aids / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013608:Tablets, Enteric-Coated
D000180:Acrylic Resins; D001786:Blood Glucose; D003692:Delayed-Action Preparations; C446821:Eudragit L100-55; D007004:Hypoglycemic Agents; D007328:Insulin; D010592:Pharmaceutic Aids; D013438:Sulfhydryl Compounds; D013608:Tablets, Enteric-Coated; C013517:ethyl cellulose; C030312:calcium polycarbophil; D002482:Cellulose; D003545:Cysteine