김경진 (에스티팜)

한빛사논문

조회183

에스티팜

J. Control. Release, Jul 13 2024, 373 S0168-3659(24)00450-4 | https://doi.org/10.1016/j.jconrel.2024.07.019 Full-cycle study on developing a novel structured micromixer and evaluating the nanoparticle products as mRNA delivery carriers

Gi-Su Na ^a, Jeong-Un Joo ^a, Joo Young Lee^b, Yejin Yun^b, Byung Kwon Kaang ^a, Joo-Sung Yang^b, Kyungjin Kim ^b, Dong-Pyo Kim^a

^aCenter for Intelligent Microprocess of Pharmaceutical Synthesis, Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea

^bResearch Center, ST Pharm, Ansan-si, Gyoenggi-do 15610, Republic of Korea

Corresponding authors : Joo-Sung Yang, Kyungjin Kim, Dong-Pyo Kim

Abstract

Achieving precise control of nanoparticle size while maintaining consistency and high uniformity is of paramount importance for improving the efficacy of nanoparticle-based therapies and minimizing potential side effects. Although microfluidic technologies are widely used for reliable nanoparticle synthesis, they face challenges in meeting critical homogeneity requirements, mainly due to imperfect mixing efficiency. Furthermore, channel clogging during continuous operation presents a significant obstacle in terms of quality control, as it progressively impedes the mixing behavior necessary for consistent nanoparticle production for therapeutic delivery and complicates the scaling-up process. This study entailed the development of a 3D-printed novel micromixer embedded with hemispherical baffle microstructures, a dual vortex mixer (DVM), which integrates Dean vortices to generate two symmetrical counter-rotating intensified secondary flows. The DVM with a relatively large mixer volume showed rapid mixing characteristics even at a flow rate of several mL min^-1 and produced highly uniform lipids, liposomes, and polymer nanoparticles in a size range (50-130 nm) and polydispersity index (PDI) values below 0.15. For the evaluation of products, SARS-CoV-2 Spike mRNA-loaded lipid nanoparticles were examined to verify protein expression in vitro and in vivo using firefly luciferase (FLuc) mRNA. This showed that the performance of the system is comparable to that of a commercial toroidal mixer. Moreover, the vigorous in-situ dispersion of nanoparticles by harnessing the power of vortex physically minimizes the occurrence of aggregation, ensuring consistent production performance without internal clogging of a half-day operation and facilitating quality control of the nanoparticles at desired scales.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-26)
연구진국내 연구진
분야 바이오·의료융합 > 바이오·의료융합 기타

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