Self-assembled nanoparticles of methotrexate conjugated O-carboxymethyl chitosan: Preparation, characterization and drug release behavior in vitro

The conjugates of O-carboxymethyl chitosan (OCM-chitosan) with methotrexate (MTX) were synthesized by carbodiimide coupling and characterized by Fourier transform infrared (FTIR), proton nuclear magnetic resonance (1H NMR) and ultraviolet spectroscopy (UV). OCM-chitosan-MTX conjugates had amphiphilic properties and their critical aggregation concentrations in aqueous media determined by fluorescence spectroscopy were 4.24 × 10−2, 1.81 × 10−2 and 0.84 × 10−2 mg/mL, respectively, responding to MTX contents of 10.8%, 16.2% and 19.3%. OCM-chitosan-MTX nanoparticles prepared by the dialysis method had nearly spherical shape and their sizes were in the range of 187.2–363.5 nm. Meanwhile, their zeta potentials ranged from −8.19 mV to −3.08 mV. Drug releases of OCM-chitosan-MTX nanoparticles were studied by the dynamic dialysis method and MTX exhibited significant sustained-release behaviors in PBS buffer solutions (pH 4.0, 7.2 and 9.0), indicating that these nanoparticles had good in vitro stability and the potential to be used as a novel drug carrier system.