Efficient drug delivery and anticancer effect of micelles based on vitamin E succinate and chitosan derivatives

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 1H 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.