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 Ca2+ ions. MTX-loaded FAchitosan (CS) nanoparticles as controls were also prepared. The chemical structure of FA-conjugated O-CMC (FAO-CMC) was confirmed by 1H-NMR and Fourier transform infrared spectroscopy. The results show that the obtained FAO-CMC nanoparticles were spherical in shape with a narrow size distribution. The encapsulation efficiency and loading capacity of MTX in the FAO-CMC nanoparticles were higher than those in the FACS nanoparticles, and the particle size of the FAO-CMC nanoparticles were also smaller than that of the control. In vitro release studies indicated that the release of MTX from FAO-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. (C) 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012