Hydrogel nanoparticle synthesis using liquid-solid separation for a more efficient, greener process

Water swollen nanoparticle synthesis methods have been fine-tuned and universally used to create materials in the medical and cosmetic industries. However, these methods often utilize toxic solvents and generate excess waste during the separation and purification processes. This work presents a protocol using an inverse nanoemulsion wherein liquid-liquid separation is replaced with liquid-solid separation, i.e. crystallization to isolate nanoparticles. Using low toxicity oils that are solids at room temperature, water-in-oil nanoemulsions can be generated at elevated temperatures, and upon removal of heat, solid-liquid separation isolates nanoparticles in the aqueous phase. Poly(ethylene glycol) diacrylate (PEG-DA) was chosen to create polymer nanogels via thermally induced radical polymerization and redox polymerization. Myristic acid inverse nanoemulsions with two molecular weights of PEG-DA (M _n = 8000 and M _n = 575) and two different stirring speeds were initially used to evaluate the system dynamics, particle size, and recovery. Scanning electron microscopy was used to evaluate the average particle size of 195.8 ± 99.95 nm for PEG-DA(8000) at 100 rpm and 208.7 ± 144.1 nm for PEG-DA(575) at 100 rpm. Myristic acid was successfully recycled to synthesize additional PEG-DA(575) based particles, achieving a consistent particle size. The sustainability of the process was evaluated using the E-factor and process mass intensity for the individual recycling steps and the overall process from the beginning to the end of life. An average E-factor of 19.7 ± 5.5 and an average process mass intensity of 173.4 ± 56.1 were determined in the presented method with oil recycling stages. Finally, lipase from porcine pancreas was encapsulated in the synthesized nanoparticles to demonstrate the versatility of the method and ability to generate particles with low thermal stability cargo. By extending the recrystallization strategy to nanoparticle synthesis, a vast improvement in the sustainability of nanoparticle synthesis compared to commonly used techniques was determined. This study paves the way for other researchers to adopt sustainable synthesis strategies with other water-soluble monomers or macromers.