Cation-induced morphological transitions and aggregation of thermoresponsive PNIPAM nanogels

Poly(N-isopropylacrylamide) (PNIPAM) nanogels are promising responsive colloidal particles that can be used in pharmaceutical applications as drug carriers. This work investigates the temperature-dependent morphological changes and agglomeration dynamics of PNIPAM nanogels in the presence of mono- and multi-valent cationic electrolytes. We described the deswelling, flocculation behaviour and aggregated morphology of PNIPAM nanogels over a range of electrolyte concentrations and temperatures revealing the critical transition points from stable suspension to spontaneous agglomeration. We demonstrated that, the flocculating ability and the response rate to form aggregates follow the order of deswelling behaviour. The TEM and AFM analysis revealed the presence of a shell-like layer with varying density in the electrolyte solutions when compared to those in aqueous medium. We observed the thermo-induced aggregation/dispersion reversibility for the Na+ and K+ at a concentration over 10 mM, for the Mg2+ and Ca2+ at a concentration over 1 mM and for the Al3+ at a concentration over 0.1 mM, which points the effective destabilization of the electrolyte system with multivalency following the Schulze–Hardy rule. Our findings were supported by applying a Debye screening model that accounts for the shielding effect of multivalent cationic electrolytes on these nanogel systems. Our experiments and the models confirmed the compression of the electric double layer as the valency and ionic strength increased with the exception of Al3+ at higher concentration which seems to disrupt the electrical double layer and cause reversal of zeta potential. Our work highlights the significant impact the presence of multivalent ions can impose on the stability and morphology of nanogels, and this understanding will help in designing responsive nanogel systems based on PNIPAMs.