The modified method integrated the principal that sodium alginate produces ionic interaction with calcium ion to form a kind of sustained-release gel into the double-emulsion method. Interferon α-1b (IFN α-1b) poly (lactic-co-glycolic) (PLGA) microspheres were prepared by the above two methods. Encapsulation efficiency

drug loading

yield and average size were used to evaluate the physicochemical properties of microspheres; Scanning electron microscope was taken to observe the outlook and internal morphology of microspheres

while the structure parameters were analyzed by the image analysis software Image J; Staining surface protein method and confocal laser scanning microscope were utilized respectively to observe protein distribution on the surface and inside the microsphere skeletons; Finally

the microspheres in vitro release pattern was studied. Compared with microspheres made by the double-emulsion method

the ones made by modified method were of the following characteristics: high encapsulation efficiency and drug loading(61.85 %，0.7243 %); less pores on the surface with lower surface porosity; less but bigger pores inside the micorspheres

with cross-sectioned porosity equal to the double-emulsion method; less proteins distributed on the surface

while more in the inner hole wall of the microspheres; The cumulated release percent was about 70 % in 30 d

with apparently less burst-release and sustained-release period over 20 d The result shows that IFN-PLGA microspheres produced by modified method were of better drug-loading and release properties.