Preparation Of Drug-loaded Nanoparticles Via Miniemulsion Polymerization And Evaluation Of Their Antineoplastic Effect

Chemotherapy is one of the most important strategies to fight against cancer.However,most anticancer drugs used in clinical cancer chemotherapy still have many problems because of their low aqueous solubility,instability and serious side effects.Nanodrugs can be efficiently targeted to the tumor cites due to the enhanced permeability and retention(EPR)effect,which greatly improves their antitumor activity and reduces their toxic side effects.Nevertheless,the complex procedures,low efficiency and low repeatability of the preparation greatly limit their potential application in clinic.Herein,we developed a novel strategy to prepare nanodrugs efficiently in a large scale for antitumor chemotherapy.Oligo(propylene carbonate)diol was first modified by acryloyl chloride to give olligo(propylene carbonate)diacrylate(PPCDA),which was used to disperse doxorubicin(DOX)and undergo miniemulsion radical polymerization with high-speed shearing in the presence of methoxy poly(ethylene glycol)acrylate as reactive emulsifier,resulting in chemophysical stable DOX-loaded nanoparticles.The diameter of these nanodrugs can be well controlled by adjusting the molar ratio of PPCDA to emulsifier,which was characterized by dynamic light scattering(DLS)and transmission electron microscope(TEM).The drug-loading efficiency and drug-loading capacity were determined by ultraviolet&visible spectrophotpmetry(UV).The DOX release behavior of the nanodrugs was investigated under physiological conditions in vitro.Cytotoxicity assay indicated that these nanodrugs exhibited excellent cytotoxic effects on cancer cells,while the similar nanoparticles without DOX loading were biocompatible.Confocal laser scanning microscopy demonstrated that the nanodrugs can be well taken into cells and present a rapid DOX release in cytoplasm.Mouse tumor model was generated by endemic injecting cancer cells.The tumor targeting ability and in vivo biodistribution of the nanodrugs in tumor-bearing mice were observed by near infrared fluorescence.The nanodrugs showed obvious EPR effect with high tumor uptake.Moreover,the drugs those were not accumulated into tumor cites can be easily cleared out from the body by liver and kidney,leading to low toxic side effects.The antitumor efficiency of the nanodrugs was also investigated using free DOX as a comparison.The results indicate that nanodrugs showed significantly high antitumor activity than free DOX with the same dose.Furthermore,the body weights of the tumor-bearing mice healed by nanodrugs were much higher than those healed by free DOX,further confirming the low toxic side effects of the nanodrugs.