Article
  • Fabrication of Microfluidic Chips Containing Porous Membrane for Continuous Production of Lipid Nanoparticles

  • Do-Hyun Oh*, **, Soo Kyung Han*, **, Young-Hyun Ryu*, **, Guk-Young Ahn*, **, Inseong Choi*, **, and Sung-Wook Choi*, **,†

  • *Biomedical and Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, Korea
    **Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, Korea

  • 다공성 막을 포함하는 미세유체칩을 이용한 항암 지질나노입자 연속 생산 공정

  • 오도현*, ** · 한수경*, ** · 류영현*, ** · 안국영*, ** · 최인성*, ** · 최성욱*, **,†

  • *가톨릭대학교 바이오메디컬화학공학과, **가톨릭대학교 생명공학과

  • Reproduction, stored in a retrieval system, or transmitted in any form of any part of this publication is permitted only by written permission from the Polymer Society of Korea.

Abstract

A polydimethylsiloxane (PDMS) microfluidic device containing a porous membrane as a middle layer was fabricated to continuously produce lipid nanoparticles (LNPs). Ethanol with lipids and water were used as discontinuous and continuous phases. Doxorubicin and lauric acid were added in the ethanol phase for tumor therapy and LNP stability. The smaller LNPs were prepared at the higher flow rate of the continuous phase by using the membrane with smaller pore size. The LNPs with a size of 87.6±3.84 nm were obtained at 0.3 mL/min of the flow rate of the continuous phase by using the membrane with a pore size of 0.02 μm. The addition of lauric acid enhanced the colloidal stability of LNPs. In addition, the LNPs with doxorubicin and lauric acid exhibited lower viability for HeLa cells and enhanced colloidal stability of LNPs. The microfluidic device with a porous membrane can be used as a general platform for the continuous production of LNPs containing mRNA, siRNA, and other therapeutic agents.


다공성 막을 중간층으로 갖는 폴리디메틸실록산 미세유체칩을 이용하여 항암 약물인 독소루비신을 함유한 지질나노입자를 연속적인 공정으로 제조하였다. 불연속상으로는 지질, 독소루비신, 및 라우릭 산을 함유한 에탄올상을, 연속상으로는 증류수를 각각 시린지펌프를 이용하여 미세유체칩에 투입하였다. 작은 기공을 갖는 다공성막을 사용하고, 연속상의 유속이 높을 수록 작은 지질나노입자가 제조되었다. 라우릭 산은 지질나노입자의 콜로이드 안정성을 증가시켜 주었고, 독소루비신과 라우릭 산의 첨가는 HeLa 암세포주에서 높은 세포 독성을 나타내었다. 이러한 미세유체칩은 다른 약물은 물론, mRNA와 siRNA를 함유한 지질나노입자제조에 응용될 수 있다.


Keywords: microfluidic, porous membrane, lipid nanoparticle, tumor therapy.

  • Polymer(Korea) 폴리머
  • Frequency : Bimonthly(odd)
    ISSN 0379-153X(Print)
    ISSN 2234-8077(Online)
    Abbr. Polym. Korea
  • 2022 Impact Factor : 0.4
  • Indexed in SCIE

This Article

  • 2022; 46(6): 722-727

    Published online Nov 25, 2022

  • 10.7317/pk.2022.46.6.722
  • Received on Mar 10, 2022
  • Revised on Jun 30, 2022
  • Accepted on Aug 8, 2022

Correspondence to

  • Sung-Wook Choi

  • *Biomedical and Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, Korea
    **Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, Korea

  • E-mail: choisw@catholic.ac.kr