Objective: To investigate the sustained release rule of doxorubicin/polylactide-grafted dextran copolymer (DOX/DEX-PLA) nanoparticles and the effect thereof in killing hepatocarcinoma cells.
Methods: DOX/DEX-PLA nanoparticles were prepared by method of emulsification & evaporation of organic solvent. Its morphology was observed by transmission electron microscopy and the encapsulating efficiency of DOX was determined by ultraviolet spectrophotometry. DOX/DEX-PLA was put in a dialysis bag to observe the releasing characteristics of DOX from DOX/DEX-PLA nanoparticles in vitro. Human liver carcinoma cells of the line HepG2 were cultured with DOX/DEX-PLA of different concentrations or the original drug of DOX as control group for 24, 36, or 48 h. MTT method was used to observe the cancer inhibition rate. BALB/c nude mice underwent subcutaneous injection of HepG2 cells at the right scapula and then randomly divided into 4 groups to undergo intravenous injection of DOX/DEX-PLA (excremental group), original drug of DOX (naked drug group), DEX-PLA (nanovector group), or normal saline (blank control group) once every 5 days for 3 times. Twenty-one days later the mice were killed with the tumors taken out to measure the weight to analyze the inhibitory effect against hepatocarcinoma cells.
Results: The DOX/DEX-PLA nanoparticles were of round or elliptical shape with the diameter of about 83 nm, and the DOX entrapment efficiency was about 67.1%. The releasing test in vitro manifested a sustained release of over 50% of DOX encapsulated in DOX/DEX-PLA nanoparticles for about 7 days. Both the DOX/DEX-PLA nanoparticles and naked drug DOX inhibited the growth of HepG2 cells with a similar inhibitory rate (51.3% vs 50.7%, P > 0.05), meanwhile the DEX-PLA nanovector failed to inhibit the HepG2 cells. In-vivo experiment showed an inhibitory rate of DOX/DEX-PLA nanoparticles on hepatocellular carcinoma xenografts of 68.56%, significantly higher than that of the naked drug DOX (48.17%).
Conclusion: DOX/DEX-PLA nanoparticles can effectively inhibit the growth of hepatocarcinoma cells.