| Approximately 1 million Americans have type I diabetes. The current long-term treatment of the disease relies predominantly on multiple daily subcutaneous (SC) injections of insulin. However, this treatment does not provide optimal metabolic control, and patients find it difficult to properly manage their blood glucose levels. Of the alternative treatment routes being studied, the oral route seems to be the ideal choice for most patients. Unlike subcutaneous injections, the oral administration of insulin would mimic the transport of insulin from the pancreas to the hepatic portal circulation as is seen with healthy non-diabetic individuals. In this way, proper liver and first-pass metabolism would be established. Unfortunately, oral insulin efficacy is almost impossible due to the harsh environment of the gastrointestinal tract.; The goal of this work was to develop an oral insulin drug delivery system as an alternative treatment for type I diabetes. By fabricating small, hydrophobic, bioadhesive polyanhydride insulin-loaded microspheres (ILMS), a delivery system was developed that would protect the encapsulated insulin from the digestive tract, promote microsphere uptake, and improve the bioefficacy of oral insulin. The insulin delivery system was tested in both healthy and type I diabetic rats. Subcutaneous injections of ILMS to diabetic rats showed that the relative bioavailability/bioefficacy of the delivery system was 90% as compared to unencapsulated insulin. A dose response was also evident with subcutaneous administration of ELMS. When tested as an oral delivery system in diabetic animals, the relative bioavailability/bioefficacy of the delivery system reached values of 25% as compared to SC injections of unencapsulated insulin. After varying the oral dosage of insulin-loaded microspheres, a dose response curve was evident. When microspheres were administered orally to fed animals, glucose levels remained constant for over 24 hours with very little subsequent weight loss, a function of proper glucose metabolism.; This work has led us to believe that bioadhesive polyanhydride insulin-loaded microspheres administered orally is a promising treatment for type I diabetes. |
