Preparation and evaluation of insulin-loaded polylactide microspheres using factorial design

The aim of this work was to study the influence of the concentration and mo lecular weight of poly(DL-lactide) (PLA) on the characteristics and in vivo biological activity of protein-loaded microspheres. At the same time, an a ttempt was made to achieve further optimization of the formulation. In the study, insulin was chosen as a model of protein drugs. Nine formulations of injectable insulin-loaded PLA microspheres were prepared using an emulsifi cation and solvent evaporation process according to a factorial design. The trapping efficiency, drug loading, and the drop percentages of blood gluco se levels at 24 hr and 72 hr in mice were used to evaluate the formulations . The results showed that PLA molecular weight and, especially, PLA concent ration exerted influences on the characteristics and in vivo biological act ivity of insulin-loaded microspheres. The drug-trapping efficiency increase d with the increase of the polymer concentration. The drug loading decrease d with the increase of the polymer concentration and was not obviously affe cted by PLA molecular weight. The drop percentage of blood glucose level at 24 hr increased with the increase of polymer concentration and molecular w eight. At 72 hr, the drop percentages of blood glucose levels were slightly increased with the increase of PLA concentration and then significantly de creased after the PLA concentration was above 150 mg/ml. Art optimized form ulation was prepared with PLA-10k at a concentration of 200 mg/ml. The expe rimental values of the response variables were close to the predicted value s. The results suggest that the in vivo release behavior should be taken in to consideration in the design of protein-loaded PLA microspheres.