Preparation, evaluation, and in vitro release of folic acid conjugated O ‐carboxymethyl chitosan nanoparticles loaded with methotrexate

To improve the targeted effect and reduce the neurotoxicity of methotrexate (MTX), folic acid (FA)‐conjugated O ‐carboxymethyl chitosan (O‐CMC) nanoparticles loaded with MTX were prepared via a crosslinking reaction between the carboxyl groups of O ‐CMC and Ca 2+ ions. MTX‐loaded FA–chitosan (CS) nanoparticles as controls were also prepared. The chemical structure of FA‐conjugated O ‐CMC (FA– O ‐CMC) was confirmed by 1 H‐NMR and Fourier transform infrared spectroscopy. The results show that the obtained FA– O ‐CMC nanoparticles were spherical in shape with a narrow size distribution. The encapsulation efficiency and loading capacity of MTX in the FA– O ‐CMC nanoparticles were higher than those in the FA–CS nanoparticles, and the particle size of the FA– O ‐CMC nanoparticles were also smaller than that of the control. In vitro release studies indicated that the release of MTX from FA– O ‐CMC nanoparticles was slower in the initial period, but the cumulative release was much higher. FA was also released from the nanoparticles; this might prove to be a potential antidote for preventing the neurotoxicity caused by MTX. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012