复乳法及其改良法制备的干扰素PLGA微球载药释药特性的对比

改良法在复乳法基础上结合了海藻酸钠与Ca2+螯合形成缓释凝胶的原理。分别用上述两法制备蛋白药物干扰素α-1b的聚乳酸聚乙醇酸(PLGA)微球,以包封率、载药量等为指标,评价其理化性质;扫描电镜观察微球内外形态,软件计算其结构参数;用表面蛋白染色、激光共聚焦显微镜观察蛋白在微球表面及骨架内的分布情况;考察微球体外释药行为。与复乳法相比,改良法所得微球有较高的包封率和载药量(61.85%,0.724 3%),表面孔洞少、孔隙率低;内部孔洞大而少,孔隙率无显著差异;蛋白更多地分布在微球内部孔洞壁上而非表面;突释显著降低,缓释时间延长至20 d以上,30 d累积释药约70%。表明改良法所得微球载药释药性能较好,释药符合缓释制剂标准。

To Compare the Drug-Loading Characteristics and Release Behavior of Interferon PLGA Microspheres Prepared by Normal and Modified Double-Emulsion Methods

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.