Scalable ionic gelation synthesis of chitosan nanoparticles for drug delivery in static mixers

The purpose of this study is to synthesize chitosan (CS) nanoparticles (NPs) by ionic gelation with tripolyphosphate (TPP) as crossslinker in static mixers. The proposed static mixing technique showed good control over the ionic gelation process and 152-376 nm CS NPs were achieved in a continuous and scalable mode. Increasing the flow rates of CS:TPP solution streams, decreasing the CS concentration or reducing the CS:TPP solution volume ratio led to the smaller particles. Sylicylic acid (SA) was used as a model drug and successfully loaded into the CS NPs during the fabrication process. Our work demonstrates that ionic gelation-static mixing is a robust platform for continuous and large scale production of CS NPs for drug delivery.