Oral Administration of Salecan-Based Hydrogels for Controlled Insulin Delivery

摘要

We present an improved type of food gum (salecan) based hydrogels for oral delivery of insulin. Structural hydrogel formation was assessed with Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction. We found that the hydrogel modulus, morphology, and swelling properties can be controlled by varying the salecan dose during hydrogel formation. Insulin was introduced into the hydrogel using a swelling-diffusion approach and then further used a drug prototype. In vitro insulin release profiles demonstrated that the release of entrapped insulin was suppressed in acidic conditions but markedly increased at neutral pH. Cell viability and toxicity tests revealed that the salecan hydrogel constructs were biocompatible. Oral administration of insulin-loaded salecan hydrogels in diabetic rats resulted in a sustained decrease of fasting plasma glucose levels over 6 h postadministration. For nondiabetic animals, the relative pharmacological bioavailability of insulin was significantly larger (6.24%, p 0.05) for insulin-loaded hydrogels compared to free insulin. These results encourage further development of salecan-based hydrogels as vehicles for controlled insulin delivery following oral administration.