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 of PNIPAM nanogels in the presence of mono- and multi-valent cationic electrolytes. We described the deswelling, flocculation, thermal reversibility 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 rate of aggregate formation follow the order of deswelling behaviour. Transmission electron microscopy and atomic force microscopy analysis revealed the presence of a shell-like layer with varying density in the multivalent electrolyte solutions when compared to those in aqueous medium. We identified a concentration threshold of the thermally induced reversible aggregation/dispersion for the PNIPAM nanogels in the presence of Na+ and K+ ions at 10 mM, for Mg2+ and Ca2+ ions at 1 mM and for Al3+ ions at 0.1 mM concentrations. Such concentration thresholds indicated 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, except for Al3+ at higher concentrations which seemed to disrupt the electrical double layer and cause reversal of zeta potential. Our work highlights the significant impact the presence of multivalent cations can impose on the stability and morphology of nanogels, and this understanding will help in designing responsive nanogel systems based on PNIPAM nanogels.

Understanding the Degradation of Core-Shell Nanogels Using Asymmetrical Flow Field Flow Fractionation.

Nanogels are candidates for biomedical applications, and core-shell nanogels offer the potential to tune thermoresponsive behaviour with the capacity for extensive degradation. These properties were achieved by the combination of a core of poly(N-isopropylmethacrylamide) and a shell of poly(N-isopropylacrylamide), both crosslinked with the degradable crosslinker N,N'-bis(acryloyl)cystamine. In this work, the degradation behaviour of these nanogels was characterised using asymmetric flow field flow fractionation coupled with multi-angle and dynamic light scattering. By monitoring the degradation products of the nanogels in real-time, it was possible to identify three distinct stages of degradation: nanogel swelling, nanogel fragmentation, and nanogel fragment degradation. The results indicate that the core-shell nanogels degrade slower than their non-core-shell counterparts, possibly due to a higher degree of self-crosslinking reactions occurring in the shell. The majority of the degradation products had molecule weights below 10 kDa, which suggests that they may be cleared through the kidneys. This study provides important insights into the design and characterisation of degradable nanogels for biomedical applications, highlighting the need for accurate characterisation techniques to measure the potential biological impact of nanogel degradation products.

Dual-responsive degradable core-shell nanogels with tuneable aggregation behaviour.

We report the synthesis of core-shell nanogels by sequential addition of thermoresponsive monomers; N-isopropylacrylamide (NIPAM) and N-isopropylmethacrylamide (NIPMAM). The aggregation behaviour of aqueous dispersions of these particles in the presence of salt can be tuned by varying the monomer ratio. The inclusion of degradable cross-linker bis(acryloyl)cystamine (BAC) allows the nanogels to degrade in the presence of reducing agent, with nanogels composed of a copolymer of the two monomers not showing the same high levels of degradation as the comparable core-shell particles. These levels of degradation were also seen with physiologically relevant reducing agent concentration at pH 7. Therefore, it is hoped that the aggregation of these nanogels will have applications in nanomedicine and beyond.

Multi-stimuli-responsive aggregation of nanoparticles driven by the manipulation of colloidal stability.

The capacity to control the dispersed or aggregated state of colloidal particles is particularly attractive for facilitating a diverse range of smart applications. For this reason, stimuli-responsive nanoparticles have garnered much attention in recent years. Colloidal systems that exhibit multi-stimuli-responsive behaviour are particularly interesting materials due to the greater spatial and temporal control they display in terms of dispersion/aggregation status; such behaviour can be exploited for implant formation, easy separation of a previously dispersed material or for the blocking of unwanted pores. This review will provide an overview of the recent publications regarding multi-stimuli-responsive microgels and hybrid core-shell nanoparticles. These polymer-based nanoparticles are highly sensitive to environmental conditions and can form aggregated clusters due to a loss of colloidal stability, triggered by temperature, pH and ionic strength stimuli. We aim to provide the reader with a discussion of the recent developments in this area, as well as an understanding of the fundamental concepts which underpin the responsive behaviour, and an exploration of their applications.