Studies on the preparation and release in vitro of the glucagon-like peptide-1 loaded long-acting injectable(microspheres)

Objective: To prepare glucagon-like peptide-1(GLP-1) loaded long-acting injectable microspheres and to evaluate release behavior in vitro of the preparation and its bioactivity.Methods: GLP-1 loaded microspheres were prepared with poly(lactic-co-glycolic acid)(PLGA) as carrier(materials) by double emulsion(w/o/w) method.Physical and chemical(characteristics) of microspheres,such as mean diameter,morphology and encapsulation efficiency were evaluated.The in vitro release behavior and its influencing factors were determined,and effect of preparation technique and in vitro release on bioacti-(vity) of GLP-1 were evaluated by in vivo animal experiments.Results: Microspheres with good shape and compactness were prepared when the concentration of NaCl was 15%(w/v) in outer water phase.The drug entrapment efficiency was more than 85%.The mean diameter was 30 μm.The accumulated release in a month could be significantly improved when using PLGA with lower inherent viscosity and adding PEG 6000 in the oil phase.The accumulated release was reached 83% during 1 month.The preparation technique did not influence on bioactivity of GLP-1,but in the course of in vitro release,the specific activity of GLP-1 in the microspheres was decreased significantly.Conclusion: GLP-1 can be encapsulated in injectable microspheres to yield one-month continuous release when using biodegradable polymers PLGA as carrier material.