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 molecular weight of poly(DL-lactide) (PLA) on the characteristics and in vivo biological activity of protein-loaded microspheres. At the same time, an attempt 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 emulsification and solvent evaporation process according to a factorial design. The trapping efficiency, drug loading, and the drop percentages of blood glucose 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 concentration exerted influences on the characteristics and in vivo biological activity of insulin-loaded microspheres. The drug-trapping efficiency increased with the increase of the polymer concentration. The drug loading decreased with the increase of the polymer concentration and was not obviously affected by PLA molecular weight. The drop percentage of blood glucose level at 24 hr increased with the increase of polymer concentration and molecular weight. At 72 hr, the drop percentages of blood glucose levels were slightly increased with the increase of PLA concentration and then significantly decreased after the PLA concentration was above 150 mg/ml. An optimized formulation was prepared with PLA-10k at a concentration of 200 mg/ml. The experimental values of the response variables were close to the predicted values. The results suggest that the in vivo release behavior should be taken into consideration in the design of protein-loaded PLA microspheres.