1. Academic Validation
  2. Size-Controllable and Monodispersed Lipid Nanoparticle Production with High mRNA Delivery Efficiency Using 3D-Printed Ring Micromixers

Size-Controllable and Monodispersed Lipid Nanoparticle Production with High mRNA Delivery Efficiency Using 3D-Printed Ring Micromixers

  • ACS Appl Mater Interfaces. 2024 Aug 5. doi: 10.1021/acsami.4c08896.
Jiwoo Hong 1 Sanghun Lee 2 Hyochan Park 2 Daehyeon Ahn 1 Jung Min Lee 1 Hyeongju Choe 2 Donghoon Kim 2 Ju Hee Kim 2 Chan Hee Chon 2
Affiliations

Affiliations

  • 1 School of Mechanical Engineering, Soongsil University, 369 Sangdo-Ro, Dongjak-Gu, Seoul 06978, Republic of Korea.
  • 2 Inventage Lab, 9F Uspce2 B, 670, Daewangpangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13494, Republic of Korea.
Abstract

Lipid nanoparticles (LNPs) are gaining recognition as potentially effective carriers for delivery of therapeutic agents, including nucleic acids (DNA and RNA), for the prevention and treatment of various diseases. Much effort has been devoted to the implementation of microfluidic techniques for the production of monodisperse and stable LNPs and the improvement of encapsulation efficiency. Here, we developed three-dimensional (3D)-printed ring micromixers for the production of size-controllable and monodispersed LNPs with a high mRNA delivery efficiency. The effects of flow rate and ring shape asymmetry on the mixing performance were initially examined. Furthermore, the physicochemical properties (such as hydrodynamic diameter, polydispersity, and encapsulation efficiency) of the generated LNPs were quantified as a function of these physical parameters via biochemical analysis and cryo-electron microscopy imaging. With a high production rate of 68 mL/min, our 3D-printed ring micromixers can be used to manufacture LNPs with diameters less than 90 nm, low polydispersity (<0.2), and high mRNA encapsulation efficiency (>91%). Despite the simplicity of the ring-shaped mixer structure, we can produce mRNA-loaded LNPs with exceptional quality and high throughput, outperforming costly commercial micromixers.

Keywords

drug delivery; lipid nanoparticles; micromixer; nucleic acids; three-dimensional (3D)-printing.

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