Chitosan nanoparticles have been extensively studied for drug and gene delivery. In this paper, monodisperse,
low molecular weight (LMW) chitosan nanoparticles were prepared by a novel method based on
ionic gelation using sodium tripolyphosphate (TPP) as cross-linking agent. The objective of this study was
to solve the problem of preparation of chitosan/TPP nanoparticles with high degree of monodispersity and
stability, and investigate the effect of various parameters on the formation of LMW chitosan/TPP nanoparticles.
It was found that the particle size distribution of the nanoparticles could be significantly narrowed
by a combination of decreasing the concentration of acetic acid and reducing the ambient temperature
during cross-linking process. The optimized nanoparticles exhibited a mean hydrodynamic diameter of
138 nm with a polydispersity index (PDI) of 0.026 and a zeta potential of +35 mV, the nanoparticles had
good storage stability at room temperature up to at least 20 days.