Fabrication of tunable, high-molecular-weight polymeric nanoparticles via ultrafast acoustofluidic micromixing

Abstract

High-molecular-weight polymeric nanoparticles are critical to increasing the loading efficacy and tuning the release profile of targeted molecules for medical diagnosis, imaging, and therapeutics. Although a number of microfluidic approaches have attained reproducible nanoparticle synthesis, it is still challenging to fabricate nanoparticles from high-molecular-weight polymers in a size and structure-controlled manner. In this work, an acoustofluidic platform is developed to synthesize size-tunable, high-molecular-weight (>45 kDa) poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA–PEG) nanoparticles without polymer aggregation by exploiting the characteristics of complete and ultrafast mixing. Moreover, the acoustofluidic approach achieves two features that have not been achieved by existing microfluidic approaches: (1) multi-step (≥2) sequential nanoprecipitation in a single device, and (2) synthesis of core–shell structured PLGA–PEG/lipid nanoparticles with high molecular weights. The developed platform expands microfluidic potential in nanomaterial synthesis, where high-molecular-weight polymers, multiple reagents, or sequential nanoprecipitations are needed.