Sustainable and Surfactant-Free Synthesis of Negatively Charged Acrylamide Nanogels for Biomedical Applications

Nanogels offer unique advantages, like high surface-to-volume ratio, scalable synthetic methods and easily tailored formulations, that allow to control size and introduce stimuli-responsive properties. Their potential for drug delivery is significant due to their biocompatibility, high drug loading capacity, and controlled and sustained drug release, but the development of greener and sustainable processes, in particular the replacement of organic solvents with water, is essential for large-scale applications. Here we report our results on the synthesis in water of covalently crosslinked acrylamide-based nanogels, both neutral and negatively charged, with varying amounts of acryloyl-L-proline, using a high-dilution radical polymerization technique without the need for surfactants. The use of a water-based synthesis resulted in nanogels with high monomer conversions and chemical yields, as well as lower polydispersity and smaller particle sizes for the negatively charged nanogels. This results in a more efficient synthetic methodology, with reduced loss of starting materials, higher potential for scalability and reduction in costs. The suitability of these nanogels for biomedical applications was supported by cytotoxicity studies showing no significant reduction in viability on a human neuroblastoma cell line.