荷载JQ1 /紫杉醇 PLGA纳米粒的制备

研究荷载JQ1/紫杉醇PLGA纳米粒的制备,并考察其对黑色素瘤细胞表面PD-L1表达情况的影响。采用乳化溶剂蒸发法制备荷载JQ1/紫杉醇的PLGA纳米粒,并对所制备的纳米粒进行粒径、形貌等理化性质表征;尾静脉注射荷载JQ-1/紫杉醇PLGA纳米粒后,考察大鼠体内的药动学参数;以B16黑色素瘤细胞为模型,应用流式细胞术分析PLGA纳米粒对B16细胞表面PD-L1表达情况的影响。结果表明,所制备的PLGA纳米粒平均粒径为210 nm,其外观呈光滑圆球状。大鼠体内单次静脉注射PLGA纳米粒后,呈二室模型分布,紫杉醇与JQ1主要的药动学参数如下:分布相半衰期为0.142 8、0.169 9 h,消除相半衰期为5.27、2.37 h,血药浓度曲线下面积为8.155、3.793 (μg·h)/mL,清除率为122.612、131.795 mL/(h·kg),表观分布体积为766.07、396.25 mL/kg。流式分析结果表明经PLGA纳米粒组处理后,可降低B16黑色素瘤细胞表面PD-L1的表达。表明所制备的PLGA纳米粒可作为紫杉醇与JQ1两种药物共递送的传输载体,有望提高免疫治疗肿瘤的效果。

Preparation of JQ1/paclitaxel-loaded PLGA nanoparticles

This study aimed to prepare JQ1/paclitaxel (PTX)-loaded poly(lactic-co-gly-colic acid) (PLGA) nanoparticles and evaluate their effect on the expression of PD-L1 on melanoma cells. The JQ1/PTX-loaded PLGA nanoparticles were prepared using the emulsion solvent evaporation method, and their physicochemical properties, such as particle size and morphology were determined. The pharmacokinetic parameters of the JQ1/PTX-loaded PLGA nanoparticles were investigated in rats after administering the rats with a tail vein injection of the nanoparticles. The effect of the nanoparticles on the expression of PD-L1 on B16 melanoma cells was analyzed using flow cytometry. The results showed that the mean particle size of the prepared nanoparticles was about 210 nm and that they appeared smooth and spherical in shape. The main pharmacokinetic parameters of PTX and JQ1 determined using a two-compartment model after administering a single intravenous injection of the nanoparticles to the rats were as follows: the half-life of the distribution phase was 0.142 8 h and 0.169 9 h; half-life of the elimination phase was 5.27 and 2.37 h; area under the curve was 8.155 and 3.793(μg·h)/mL; clearance was 122.612 and 131.795 mL/(h·kg); and apparent volume of distribution was 766.07 and 396.25 mL/kg, respectively. Flow cytometry showed that the nanoparticles could reduce the expression of PD-L1 on B16 melanoma cells. Thus, the prepared PLGA nanoparticles can be used as carriers for the co-delivery of PTX and JQ1, which is expected to improve the effect of immunotherapy on tumors.