Formulation Optimization of Alginate mPEG-b-PLGA Nanoparticles by Box-Behnken Response Surface Method / 中国药学杂志

ABSTRACT

OBJECTIVE: To optimize the formulation of alginate mPEG-b-PLGA nanoparticles by Box-Behnken response surface method. METHODS: Using synthetic 10% mPEG-b-PLGA as nanoparticles matrix materials, the insulin-loaded alginate mPEG-b-PLGA nanoparticles were prepared by modified double emulsion-solvent evaporation method.To optimize the formulation,the mass ratio of insulin to polymer,the volume ratio of oil phase to external water and the concentration of poloxamer 188(F68) were selected as independent variables, with encapsulation efficiency(EE%), loading capacity(LC%) as the dependent variables.The formula was optimized by Box-Behnken design and response surface methodology.The particles size, polydispersity index(PDI), Zeta potential and morphology of optimized nanoparticles were measured by dynamic light scattering(DLS), electrophoretic light scattering(ELS) and transmission electron microscope(TEM), respectively.The in vitro release profile of nanoparticles was investigated. RESULTS: The optimal formulation was as followsthe mass ratio of insulin to mPEG-b-PLGA was 14.67100, the oil phase to external water ratio was 13.32 and F68(W/V) concentration was 2.01%, respectively. The entrapment efficiency, the loading capacity, average particles size and Zeta potentials were(83.61±0.38)%,(10.90±0.23)%,(271.8±3.5) nm and(-54.27±2.75) mV, respectively, which correspond closely to the predicted values.The optimized insulin-loaded nanoparticles performed good sustained release property in pH 7.4 medium. CONCLUSION: The Box-Behnken design and response surface methodology is an effective and efficient method, which can be applied in the formula optimization of alginate mPEG-b-PLGA nanoparticles preparation.The optimized nanoparticles can be served as a promising insulin or proteins drug nanocarriers for its good sustained release property.