In vitro/in vivo evaluation of microspheres containing Exendin-4 for treatment of type 2 diabetes mellitus / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare poly(lactic-co-glycolic acid) (PLGA) microspheres of Exendin-4 and evaluate its characteristics. METHODS: Exendin-4 microspheres were prepared by different preparation methods (W/O/W, S/O/O and S/O/W method) and characterized for encapsulation efficiency by high-performance liquid chromatography (HPLC), particle size by laser particle size analyzer, surface morphology by scanning electron microscopy (SEM), and Exendin-4 stability by circular dichroism (CD). Release rate in vitro was determined, and the microspheres were administered subcutaneously to type 2 diabetic rats to determine its pharmacokinetics and pharmacodynamics. RESULTS: Exendin-4 was successfully encapsulated into PLGA microspheres by W/O/W method. The average size was 25-30 μm. Exendin-4 encapsulation efficiency was 82.2%. CD confirmed that the structural integrity of the peptide was intact. The burst release in 24 h was 15.2% and the cumulated release in 28 d was up to 90% in vitro. Animal study demonstrated the drug release from microspheres in vivo and in vitro had a good correlation(r=0.9623) and the blood glucose level was controlled for 4 weeks by Exendin-4 microspheres. CONCLUSION: The PLGA microspheres can be used for the controlled delivery of Exendin-4.