Objective: To optimize preparation technology of genistein-loaded MePEG-PLGA namo-micelle with modified spontaneous emulsification solvent diffusion method. Method: Firstly

orthogonal design was used to preliminary screen prescription

and determine main influence factors. Then optimized prescription by central composite design (CCD) and response surface methodology (RSM). Main influence factors included concentration of genistein micelles in organic phase

concentration of MePEG-PLGA in organic phase and the ratio of water phase to organic phase

evaluation parameters included entrapment efficiency

drug loading and average diameter. Data were simulated using multi-linear regression and second-order polynomial equation. The better technology condition was predicted by response surface method. Result: According to the optimal formulation

the entrapment efficiency

the drug loading and the average diameter of the prepared namo-micelle were 84.43%

2.63%

63.7 nm

respectively. Conclusion: Combined of orthogonal design with CCD and RSM was a convenient and feasible method to optimize preparation technology of genistein-loaded MePEG-PLGA namo-micelle and model developed in this study are proved to be predictable.