Abstract:

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.

Key words: paclitaxel, JQ1, PLGA nanoparticles, melanoma