Developing a simple and efficient approach to formulate biodegradable nanoparticles for intravenous delivery of sodium valproate (a hydrophilic small molecule drug chronically used in epileptic patients), is the principal objective of the current study. To fabricate particles via ionotropic gelation approach, a polycation polymer (chitosan) along with a polyanion (tripolyphosphate) was utilized in the presence of sodium valproate, and the Taguchi experimental design method was drawn upon so as to determine the optimum conditions of nanoparticle generation. In the following step, the researchers investigated sodium valproate-loaded nanoparticles to explore various features of the nanoparticles including drug loading parameters, particle size distribution, zeta-potential, morphology, stability, yield, and in vitro drug release profile. Nanoparticles with sizes of 63 +/- 1 nm (number-based) and 79 +/- 3.21 (volume-based) were obtained with slightly negative zetapotential, which was more positive in drug-loaded nanoparticles than the unloaded ones. The TEM imaging of the hydrogel nanoparticles manifested spherical shapes and corroborated the size achieved via particle size analyzer. The loading efficiency, loading amount, and loading ratio were determined to be 21.81 +/- 3.90%, 10.31 +/- 1.82 (mg sodium valproate/g nanoparticle) and 23.70 +/- 4.54%, respectively, in optimum conditions. Moreover, there was observed a gradual drug release for nearly a week consisting, in average, about 94.64 +/- 2.71% of the nanoparticles' drug content. In a nutshell, the present study introduces a practical, simple, and effective ionotropic gelation approach to generate sodium valproate-loaded nanoparticles, leaving open a window of promising prospects in the field of intravenous long-term delivery of this chronically used drug. (c) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011