E?cient drug delivery and anticancer e?ect of micelles based on vitamin E succinate and chitosan derivatives

摘要

Nanocarriers have emerged as a promising cancer drug delivery strategy. Multi-drug resistance caused by overexpression of multiple-drug excretion transporters in tumor cells is the major obstacle to successful chemotherapy. Vitamin E derivatives have many essential functions for drug delivery applications, such as biological components that are hydrophobic, stable, water-soluble enhancing compounds, and anticancer activity. In addition, vitamin E derivatives are also effective mitocan which can overcome multi-drug resistance by binding to P glycoproteins. Here, we developed a carboxymethyl chitosan/vitamin E succinate nano-micellar system ( O -CMCTS-VES). The synthesized polymers were characterized by Fourier Transform IR, and 1 H NMR spectra. The mean sizes of O -CMCTS-VES and DOX-loaded nanoparticles were around 177?nm and 208?nm. The drug loading contents were 6.1%, 13.0% and 10.6% with the weight ratio of DOX to O -CMCTS-VES corresponding 1:10, 2:10 and 3:10, and the corresponding EEs were 64.3%, 74.5% and 39.7%. Cytotoxicity test, hemolysis test and histocompatibility test showed that it had good biocompatibility in vitro and in vivo . Drug release experiments implied good pH sensitivity and sustained-release effect. The DOX/ O -CMCTS-VES nanoparticles can be efficiently taken up by HepG2 cancer cells and the tumor inhibition rate is up to 62.57%. In the in vivo study by using H22?cells implanted Balb/C mice, DOX/ O -CMCTS-VES reduced the tumor volume and weight efficiently with a TIR of 35.58%. The newly developed polymeric micelles could successfully be utilized as a nanocarrier system for hydrophobic chemotherapeutic agents for the treatment of solid tumors.