pH/redox responsive core cross-linked nanoparticles from thiolated carboxymethyl chitosan for in vitro release study of methotrexate

A novel amphiphilic thiolated carboxymethyl chitosan was synthesized. It self-assembled into disulfide bond cross-linked nanoparticles in deionized water. The TEM showed that these nanoparticles had a core-shell structure with an average diameter of 160nm. Dynamic light scattering showed that the nanoparticles were stable in water solution. The particle size changed with pH values and GSH concentrations, and reached a maximum diameter at pH 7.0 and 20 mM GSH respectively, exhibiting an obvious pH/redox responsibility. Methotrexate was encapsulated in nanoparticles reaching encapsulation efficiency as much as 43.4%. Release profiles of methotrexate showed a release rate of 19 wt% in pH 7.4 buffer containing 10 mu M GSH, whereas as high as 93 wt% in pH 5.0 buffer containing 20 mM GSH, indicating that the nanoparticles may be used for tumor-specific drug release. The anticancer activity test in vitro showed that the inhibition rate of methotrexate-loaded nanoparticles against HeLa cells reached 90%. (C) 2014 Elsevier Ltd. All rights reserved,