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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.

The control of COVID-19 across the world requires the formation of a range of interventions including vaccines to elicit an immune response and immunomodulatory or antiviral therapeutics. Here, we demonstrate the nanoparticle formulation of a highly insoluble drug compound, niclosamide, with known anti SARS-CoV-2 activity as a cheap and scalable long-acting injectable antiviral candidate.

The formation of inorganic–organic magnetic nanocomposites using reactive chemistry often leads to a loss of super-paramagnetisim when conducted in the presence of iron oxide nanoparticles. We present here a low energy and chemically-mild process of co-nanoprecipitation using SPIONs and homopolymers or amphiphilic block copolymers, of varying architecture and hydrophilic/hydrophobic balance, which efficiently generates near monodisperse SPION-containing polymer nanoparticles with complete retention of magnetism, and highly reversible aggregation and redispersion behaviour. When linear and branched block copolymers with inherent water-solubility are used, a SPION-directed nanoprecipitation mechanism appears to dominate the nanoparticle formation presenting new opportunities for tailoring and scaling highly functional systems for a range of applications.

An in situ forming implant (ISFI) for drug delivery combines the potential to improve therapeutic adherence for patients with simple administration by injection. Herein, we describe the preparation of an injectable nanocomposite ISFI composed of thermoresponsive poly(N-isopropylacrylamide) based microgels and solid drug nanoparticles. Monodisperse poly(N-isopropylacrylamide) or poly(N-isopropylacrylamide-co-allylamine) microgels were prepared by precipitation polymerisation with mean diameters of approximately 550 nm at 25 °C. Concentrated dispersions of these microgels displayed dual-stimuli responsive behaviour, forming shape persistent bulk aggregates in the presence of both salt (at physiological ionic strength) and at body temperature (above the lower critical solution temperature of the polymer). These dual-stimuli responsive microgels could be injected into an agarose gel tissue mimic leading to rapid aggregation of the particles to form a drug depot. Additionally, the microgel particles aggregated in the presence of other payload nanoparticles (such as dye-containing polystyrene nanoparticles or lopinavir solid drug nanoparticles) to form nanocomposites with high entrapment efficiency of the payload. The resulting microgel and solid drug nanoparticle nanocomposites displayed sustained drug release for at least 120 days, with the rate of release tuned by blending microgels of poly(N-isopropylacrylamide) with poly(N-isopropylacrylamide-co-allylamine) microgels. Cytotoxicity studies revealed that the microgels were not toxic to MDCK-II cells even at high concentrations. Collectively, these results demonstrate a novel, easily injectable, nanocomposite ISFI that provides long-term sustained release for poorly water-soluble drugs without a burst release.