Design and in vivo evaluation of a patch delivery system for insulin based on thiolated polymers

PurposeThe aim of this study was to develop and evaluate a novel three-layered oral delivery system for insulin in vivo.MethodsThe 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.ResultsThe mucoadhesive layer, exhibiting a diameter of 2.5 mm and a weight of 5 mg, 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 6 h. 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 ± 6.2 ng/ml and was reached 6 h after administration. The relative bioavailability of orally administered patch system versus subcutaneous injection was 2.2%.ConclusionThe results indicate that the patch system provides enhancement of intestinal absorption and thereby offers a promising strategy for peroral peptide delivery.