Ionically crosslinked chitosan particles with submicron dimensions attract widespread interest as materials
for controlled release. To this end, we have examined the formation and dissolution of nanoparticles
prepared by crosslinking chitosan with pyrophosphate (PPi). The formation of these particles required a
critical PPi concentration (which increased with the chitosan concentration), and their z-average hydrodynamic
diameters could be predictably tuned from roughly 60 to 220 nm by varying the concentration of
the parent chitosan solutions. Unlike the nanoparticles crosslinked with the commonly used tripolyphosphate
(TPP), which coagulated and precipitated when TPP was in excess, the chitosan/PPi nanoparticles
remained colloidally stable even at high PPi concentrations. Moreover, the analysis of their dissolution
revealed hysteresis in the particle formation/dissolution cycle, where portions of the crosslinked
chitosan/PPi complexes remained stably intact at PPi concentrations below those required for their formation.
This irreversible behavior was surmised to reflect the cooperativity of chitosan/PPi binding and
was qualitatively modeled using the Bragg–Williams theory.