Study On The Sustained-release Exendin-4/CS-NaAlg Microspheres

Exendin-4 is the most widely used in the treatment of diabetes. But similar to the other protein polypeptide drugs, Exendin-4 is destroyed easily in the gastric environment and degradaed by the gastrointestinal enzymes. So there are some limitations in improving the bioavailability of the Exendin-4. At present, to achieve the purpose of lowering blood glucose, Exendin-4 is mainly administrered by subcutaneous injection. No doubt that regular administration not only gives suffering to the patients, but also causes hypoglycemia. Therefore, the development of a new dosage of Exendin-4 has become particularly important. Long-acting released micropheres of Exendin-4 is currently developed direction. The formulation not only makes the patients avoid the painful subcutaneous injection and the drug dependence, but also protects Exendin-4 from the digestive enzymes damage.What we study is that, the Exendin-4/CS-Na Alg microspheres were prepared via invers emulsion dispersion-ionomer legitimate. The Exendin-4/CS-Na Alg microspheres were detected by scanning electron microscope(SEM). The pictures showed that the resultant microspheres were cylindrical spherical, smooth, uniformly dispersed, the particle size was about 100 um. The study found that the resultant entrapment of the microspheres was 68.7%. In vitro release of microspheres test found that, in low p H environment, such as gastric fluid, the microspheres were insoluble and shrinked, which could effectively prevent the release of Exendin-4. As the p H increase, the microspheres became soluble and swelled, rendering it more permeable for release of the entrapped Exendin-4. The MTT found that the resultant microspheres is not toxic to cells, indicating we should do further research on hypoglycemic effects of Exendin-4/CS-Na Alg microspheres in animals.By intraperitoneal injection of a predetermined dose of alloxan,we established the Type 2 Diabetes Mellitus male Wistar rats model, we studied the effect on hypoglycemic of the resultant Exendin-4/CS-Na Alg microspheres.The results showed that, the relative blood glucose reduced significantly from 100% to 40% when given to the resultant microspheres. It also showed that Exendin-4 in the microspheres still maintained its activity.In summary,Exendin-4/CS-Na Alg microspheres as one of oral administration dosages had potential research value and application prospect.