Study On The Sustained-Release Liraglutaide/CS Microspheres

Liraglutide, as a GLP-1 receptor agonist drugs, was recently approved in Europe and Japan and was also the first human GLP-1 receptor agonists to be widely used in clinical because of high structural homology with human GLP-1.Because liraglutide belongs to polypeptide drugs which are easily destroyde in low p H and enzyme, oral bioavailability is very low. Although the daily subcutaneous injection of drug absorption process is slow, relatively long duration, the blood glucose can be controlede in physical level. We all konw that injections often give patients a great pain, and at the same time there is a risk of infection,so the development of new drug delivery method is helpful to liraglutide to be more widely used. Microspheres is a new development direction for polypeptide drugs,which makes liraglutide keep from enzymatic destruction, but also enable patients to reduce the pain of injection, reduce drug dependence.Chitosan, a kind of natural polymer material, has the characteristics of safety, non toxicity and good biocompatibility. Chitosan molecules with some positive charge can form a grid structure in the role of the crosslinking agent,whch is effective in the drug molecules adsorbed on the surface or the drug wrapped in them. In the gastrointestinal tract, the chitosan molecules can be the barrier of the drug, which keeps liraglutide away from the hydrolysis of the low p H and digestive enzyme. The chitosan molecules can also adhere to the intestinal mucosa and prolong the residence time of the drug in the small intestine, achieving the purpose of site-specific drug delivery, so it can effectively improve the absorption of drugs in the human body and its oral bioavailability.In this study, chitosan was used as the main material to prepare drug-loaded microspheres, in order to solve the dependence of the long-term injection drug administration of Liraru peptide drugs in diabetes patients. The experimental results show that the cell toxicity of liraglutide / chitosan microspheres is very small, and can effectively promote the insulin release of INS-1cell; and the results of animal experiments, the drug can improve the liraglutide effect in rats, but the shortcomings mainly in the control of blood sugar levels did not reach to the effect of Liraglutide injection.Although the subject did not achieve the desired effect, but obviously liraglutide / chitosan microspheres can improve the liraglutide in the dwell time of rats in vivo, if a little modification can make the release of liraglutide achieve the best dose of the drug concentration in a short time, and be able to maintain the effective concentration for a long time, will undoubtedly bring great for the convenience of patients with diabetes mellitus.