Robust Manufacturing of Lipid-Polymer Nanoparticles through Feedback Control of Parallelized Swirling Microvortices

Abstract

A variety of therapeutic and/or diagnostic nanoparticles (NPs), or nanomedicines, have been formulated for improved drug delivery and imaging applications. Microfluidic technology enables continuous and highly reproducible synthesis of NPs through controlled mixing processes at the micro- and nanoscale. Yet, the inherent low-throughput remains a critical roadblock, precluding the probable applications of new nanomedicines for clinical translation. Here we present robust manufacturing of lipid-polymer NPs (LPNPs) through feedback controlled operation of parallelized swirling microvortex reactors (SMRs). We demonstrate the capability of a single SMR to continuously produce multicomponent NPs and the high-throughput performance of parallelized SMRs for large-scale production (1.8kg/d) of LPNPs while maintaining the physicochemical properties. Finally, we present robust and reliable manufacturing of NPs by integrating the parallelized SMR platform with our custom high-precision feedback control system that addresses unpredictable disturbances during the production. Our approach may contribute to efficient development and optimization of a wide range of multicomponent NPs for medical imaging and drug delivery, ultimately facilitating good manufacturing practice (GMP) production and accelerating the clinical translation.

Graphical abstract