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目的制备葡激酶突变体(K35R,DGR)的聚乳酸-羟基乙酸(PLGA)微球,使其在包封和释放过程中都能保持活性。方法使用复乳溶剂挥发法制备DGR的PLGA微球,研究了搅拌速度、PLGA浓度、内水相和外水相中的添加剂对蛋白包封率以及微球性质的影响,并进行了DGR微球的体外和体内释放试验。结果2%聚乙烯醇可以有效抑制超声乳化时DGR在水/二氯甲烷界面上的变性,将DGR的活性回收率从16%提高到几乎100%。在外水相中加入NaCl可以显著提高蛋白包封率,同时对微球的粒径分布和表面形态也产生了重要影响。DGR微球的体外释放呈现两个时相,15d释放大约DGR总活性的50%。DGR微球在体内持续释放5d。结论制备的PLGA微球,DGR包封率高,稳定性较好,是DGR的良好载药系统。
Objective To prepare polylactide-glycolic acid (PLGA) microspheres of staphylokinase mutants (K35R, DGR) to maintain their activity during encapsulation and release. Methods The PLGA microspheres of DGR were prepared by the complex emulsion solvent evaporation method. The effects of stirring speed, PLGA concentration, additives in the inner and outer aqueous phases on the encapsulation efficiency of the protein and properties of the microspheres were investigated. In vitro and in vivo release test. Results 2% polyvinyl alcohol could effectively inhibit the denaturation of DGR on the water / dichloromethane interface during phacoemulsification and increase the activity recovery of DGR from 16% to almost 100%. The addition of NaCl into the external aqueous phase can significantly improve the protein encapsulation efficiency, and also have an important influence on the particle size distribution and surface morphology of the microspheres. In vitro release of DGR microspheres exhibits two phases, which release approximately 50% of the total DGR activity at 15 days. DGR microspheres in the body sustained release 5d. Conclusion PLGA microspheres prepared, DGR encapsulation efficiency, good stability, is a good DGR drug delivery system.