Experimental and model study of the formation of chitosan-tripolyphosphate-siRNA nanoparticles

Chitosan-tripolyphosphate (TPP) nanoparticles have received great interest as a drug delivery system due to the simple and mild procedure of ionic gelation and the biocompatibility of chitosan. We have studied the formation of chitosan nano- and microparticles through ionic gelation with TPP in the absence and presence of NaCl, by measuring the kinetics of formation, particle size, and zeta potential. Depending on the experimental conditions (concentrations of chitosan and TPP and the presence or absence of NaCl), particle formation displays an exponential or a sigmoidal time dependency. In order to explain the kinetics measurements, we have set up a simple kinetics model involving four different species. The model is constructed on the basis of previously proposed mechanisms of particle formation and our measurements of particle size and kinetics of formation. The model can simulate all the different time dependencies of particle formation. We also determined the effect of small interfering RNA (siRNA) on the rate of particle formation, but apparently siRNA has little or no influence on particle formation when TPP is present.