Microfluidic Tesla mixer with 3D obstructions to exceptionally improve the curcumin encapsulation of PLGA nanoparticles

Nanoprecipitation is a well-established method that involves straightforward and rapid mixing to encapsulate therapeutic drugs into polymeric nanoparticles (NPs). Microfluidic mixing has emerged as a powerful method for achieving small and uniform NPs, which are particularly challenging with conventional bulk mixing. Various geometries have been developed to enhance mixing efficiency in microfluidics. Efficient fluid mixing using Tesla structures has been successfully established, but the integration of 3D obstructions into Tesla structures has not yet been reported. Our focus is on enhancing mixing efficiency using a 3D microfluidic Tesla mixer, which was achieved by integrating 3D obstructions (triangular prism, cylinder, and cone) into Tesla structures fabricated by 3D printing. We examine the impact of the Tesla structure and geometrical characteristics of the obstructions on the flow phenomenon and chaotic mixing via computational fluid dynamics (CFD) simulations and experiments. We demonstrate that the Tesla mixer with cone-shaped obstructions significantly improves the mixing efficiency, resulting in a remarkable 99.4 % mixing index within 400 ms at a flow rate of 50 mL/h. We use the optimal 3D microfluidic Tesla mixer to control the formulation of small and uniform poly(lactic-co-glycolic) acid (PLGA) NPs by varying the solvent type, PLGA concentration and molecular weight, and flow condition. Importantly, curcumin-encapsulated PLGA NPs (Cur-PLGA NPs) with high drug encapsulation efficiency (up to 68.40 %) and exceptional curcumin loading (up to 43.01 %) are produced using our device with high mixing efficiency. Furthermore, in vitro studies on curcumin drug release with different degradation rates as pH changes reveal that our 3D microfluidic Tesla mixer has considerable potential as a scalable production device for drug delivery applications with a highly unique efficacy.