Formation mechanism of monodisperse, low molecular weight chitosan nanoparticles by ionic gelation technique

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.