Microfluidic-driven mixing of high molecular weight polymeric complexes for precise nanoparticle downsizing

Chitosan (CHIT) and hyaluronic acid (HA) are two polysaccharides (PSs) with high value in several biomedical applications. In this study, we present a microfluidic method to synthetize CHIT-HA NPs to overcome the disadvantages of the dropwise approach generally used for nanoprecipitation of polyelectrolyte complexes. The proposed microfluidic approach enables to generate monodisperse suspensions of NPs with ≈100 nm of size compared to the dropwise method that generated ≈2 times bigger NPs. Finally, we evaluated the potential of obtained NPs in an inflammatory scenario. The treatment with NPs led to the reduction of the main inflammatory molecules produced by macrophages (PGE2, IL-6, IL-8, MCAF and TNF-α) and fibroblasts (IL-1 α, PGE2, TNF-α) stimulated with lipopolysaccharide or conditioned medium, respectively. This study demonstrates that our approach can be used to enhance the synthesis of nanocarriers based on bioactive macromolecules. Chitosan (CHIT) and high molecular weight hyaluronic acid (HA) nanoparticles (NPs) were synthetized by microfluidic or dropwise approach. The microfluidic chip allowed to generate NPs with half the size compared to the one obtained with the dropwise method. Afterwards, NPs' ability to suppress inflammation was assessed in vitro. Results showed that microfluidic-derived NPs conferred overall a stronger protection against inflammation induced in macrophages and fibroblasts cells. [Display omitted]