Scalable synthesis of lipid nanoparticles for nucleic acid drug delivery using an isometric channel-size enlarging strategy  

作　　者：Zesen Ma Haiyang Tong Sijin Lin Li Zhou Demeng Sun Baoqing Li Changlin Tian Jiaru Chu 

机构地区：[1]Department of Precision Machinery and Precision Instrumentation,University of Science and Technology of China,Hefei 230027,China [2]Key Laboratory of Precision Scientific Instrumentation of Anhui Higher Education Institutes,University of Science and Technology of China,Hefei 230027,China [3]Science Island Branch,Graduate School,University of Science and Technology of China,Hefei 230026,China [4]Anhui Provincial Key Laboratory of High Field Magnetic Resonance Imaging,High Magnetic Field Laboratory,Hefei Institute of Physical Science,Chinese Academy of Sciences,Hefei 230031,China [5]Anhui Provincial Engineering Laboratory of Peptide Drugs,University of Science and Technology of China,Hefei 230027,China [6]School of Biomedical Engineering,Division of Life Sciences and Medicine,University of Science and Technology of China,Suzhou 215127,China

出　　处：《Nano Research》2024年第4期2899-2907,共9页纳米研究（英文版）

基　　金：supported in part by Collaborative Innovation Program of Hefei Science Center,CAS(No.2022HSCCIP001);Anhui Province Key Laboratory of High Field Magnetic Resonance Imaging(No.KFKT-2022-0003);Joint Research Fund for Overseas Chinese,Hong Kong and Macao Young Scholars(No.51929501);National Key R&D Program of China(No.2022YFF0705002).

摘　　要：Lipid nanoparticles(LNPs)have emerged as highly effective delivery systems for nucleic acid-based therapeutics.However,the broad clinical translation of LNP-based drugs is hampered by the lack of robust and scalable synthesis techniques that can consistently produce formulations from early development to clinical application.In this work,we proposed a method to achieve scalable synthesis of LNPs by scaling inertial microfluidic mixers isometrically in three dimensions.Moreover,a theoretical predictive method,which controls the mixing time to be equal across different chips,is developed to ensure consistent particle size and size distribution of the synthesized LNPs.LNPs loaded with small interfering RNA(siRNA)were synthesized at different flow rates,exhibiting consistent physical properties,including particle size,size distribution and encapsulation efficiency.This work provides a practical approach for scalable synthesis of LNPs consistently,offering the potential to accelerate the transition of nucleic acid drug development into clinical application.

关 键 词：lipid nanoparticles nucleic acid delivery MICROFLUIDICS scalable synthesis consistent particle size 

分 类 号：O62[理学—有机化学]