光敏自供氧微球的制备及其对类风湿关节炎成纤维样滑膜细胞的光动力作用研究

Preparation of oxygen self-supplying phototherapy microspheres and its photodynamic effects on fibroblast-like synoviocytes of rheumatoid arthritis

目的:制备光敏自供氧微球,考察其理化性质并研究其对类风湿关节炎成纤维样滑膜细胞的作用。方法:以聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]为载体材料,血卟啉单甲醚(hematoporphyrin monomethyl ether,HMME)为光敏剂,过氧化钙(CaO2)为产氧物质,采用油包油乳化溶剂挥发法制备光敏自供氧微球,并对微球的形貌、粒径、包封率和体外释放行为等性质进行了考察;同时采用人类风湿关节炎成纤维样滑膜细胞MH7A为研究对象,考察光敏自供氧微球在细胞内的产氧能力及产单线态氧能力,并研究其在光动力介导下对细胞生长的抑制作用。结果:制备得到的光敏自供氧微球平均粒径为(436.33±23.52)nm;HMME及CaO2的包封率分别为(62.82±1.77)%和(71.14±3.75)%且缓释性能良好;其可有效改善MH7A细胞的缺氧状态,并在细胞内产生大量活性氧物质,在光动力的联合作用下显著抑制MH7A细胞的活力。结论:采用油包油乳化溶剂挥发法成功制备光敏自供氧微球,与光敏微球相比,其可有效改善细胞中的氧气供应并增效光动力作用,显著抑制MH7A细胞的增殖,控制类风湿关节炎的病理进展。

Objective:To prepare oxygen self-supplying phototherapy microspheres and investigate their cytotoxicity on fibroblast-like synoviocytes of rheumatoid arthritis.Methods:The oxygen self-supplying phototherapy microspheres were prepared by O/O emulsification solvent evaporation method using poly(lactic-co-glycolic acid)as carrier material,hematoporphyrin monomethyl ether as photosensitizer and calcium peroxide as oxygen-producing material.The properties of the microspheres such as morphology,particle size,encapsulation efficiency and in vitro release were investigated,respectively.Human rheumatoid arthritis fibroblast-like synoviocytes cells(MH7 A)were used to investigate the intracellular oxygen production capacity and singlet oxygen production capacity as well as the effect of oxygen self-supplying phototherapy microspheres.Results:The average size of oxygen self-supplying phototherapy microspheres was(436.33±23.52)nm and the encapsulation efficiencies of HMME and CaO2 were(62.82±1.77)%and(71.14±3.75)%,respectively.The oxygen self-supplying phototherapy microspheres improved the hypoxia state of cells and generated a large amount of reactive oxygen species,significantly inhibited the viability of MH7 A cells.Conclusion:The oxygen self-supplying phototherapy microspheres were successfully prepared by O/O emulsification solvent evaporation method.Compared with phototherapy microspheres,it can effectively improve the oxygen supply and enhance the effects of photodynamic therapy to inhibit the proliferation of cells,thereby controlling the pathological progress of rheumatoid arthritis.