Surface-modified PLGA nanoparticles with PEG/LA-chitosan for targeted delivery of arsenic trioxide for liver cancer treatment: Inhibition effects enhanced and side effects reduced

摘要

Arsenic trioxide (As2O3), an effective drug for leukemia, is limited to be used for solid tumor treatment due to its high side effects. In this study, polyethylene glycol (PEG) and lactobionic acid (LA) modified chitosan (PLC) was synthesized and was used to coat poly(lactide-co-glycolide) (PLGA) nanoparticles for encapsulation and targeted release of As2O3 in liver cancer treatment. The As2O3-loaded PLGA/PLC nanoparticles (As2O3-PLGA/PLC NPs) were fabricated through double emulsion-solvent evaporation method and were optimized by orthogonal tests. As2O3-PLGA/PLC NPs presented suitable physical stability, positive charge, high encapsulation efficiency and drug loading, and good biocompatibility. As expected, the NPs can quickly release enough dose of As2O3 in a short time and then sustain the drug concentration. The As2O3-PLGA/PLC NPs showed effective inhibition of SMMC-7721 cells while having lower cytotoxicity against normal human liver cells (LO2 cells). Furthermore, In vivo study showed that the NPs did not present toxic effects on kidney and liver, but showed relatively high growth inhibition effect on liver tumor. Therefore, this PLGA/PLC NPs could be an effective and safe drug delivery system for liver cancer chemotherapy.