载紫杉醇缓释微球的制备及其体外抑瘤效果的观察

Preparation of paclitaxel-loaded PLGA microspheres and their in vitro inhibitory effect on tumor cells

目的应用乳酸-羟基乙酸共聚物(PLGA)制备载紫杉醇(PTX)PLGA微球,探讨其理化性质及其体外抑瘤效果。方法采用双乳剂挥发法制备PTX-PLGA微球,扫描电镜及光学显微镜观察其外观形态,测定微球径线。高效液相色谱法评价PTX-PLGA微球载药率及其包封率。培养卵巢癌SKOV3细胞株,并设空白对照组、生理盐水组、PLGA微球悬液组、紫杉醇注射液组和PTX-PLGA微球悬液组,应用MTT法检测不同处理组在不同时间细胞的生长抑制情况,倒置显微镜下观察肿瘤细胞凋亡形态。结果 PTX-PLGA微球大小均匀,表面光滑无粘连,平均直径为(2.00±0.19)μm,载药率约为5.68%,包封率为81.10%。给药72 h后药物浓度为1×105mol/L时,PTX-PLGA组的卵巢癌细胞增殖明显受到抑制(P<0.05)。结论本法制备的PTX-PLGA微球性质稳定,对卵巢癌细胞的抑制作用具有一定缓释效果。

Objective To prepare poly（lactic-co-glycolic acid）（PLGA）microspheres containing paclitaxel（PTX）,and to evaluate their physicochemical properties and in vitro inhibitory effect on tumor cells.Methods PLGA microspheres containing PTX were prepared by the double emulsion evaporation method.The morphology and grain diameters of microspheres were observed by a scanning electron microscope（SEM）and an optical microscope.HPLC was used to detect the drug loading amount and encapsulation efficiency.Cultured cells of the human ovarian carcinoma cell line SKOV3 were treated with RPMI1640 as blank controls,normal saline（NS）,PLGA,PTX and PTX-PLGA microspheres.The proliferation of SKOV3 cells was determined by MTT assay and the morphological change was observed under an inverted microscope.Results The microspheres with a mean particle size of（2.00±0.19）μm were uniform and smooth.Drug loading amount and encapsulation efficiency were 5.68% and 81.10%,respectively.Proliferation of SKOV3 cells was significantly inhibited by PTX-PLGA microspheres at 1×105mol/L in 72 h（P0.05）.Conclusion PTX-PLGA microspheres prepared by this method are stable and have sustained release effect on inhibiting proliferation of SKOV3 cells in vitro.