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.