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Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Microfluidic Assembly of Lipid Nanoparticles for Delivery of Antisense Oligonucleotides

Author(s): Yulin Zhou, Zhaoli Meng, Tianqi Guo, Yige Fu, Robert J. Lee and Jing Xie

Volume 15, Issue 9, 2014

Page: [823 - 828] Pages: 6

DOI: 10.2174/1389201015666141020155417

Price: $65

Abstract

Microfluidically (MF) synthesized lipid nanoparticles (LNPs) for antisense oligonucleotides (ODN) delivery have been shown to be superior to those prepared by bulk mixing (BM). In this study, a 5-inlet MF chip was used to synthesize LNPs loaded with LOR-2501, an antisense ODN targeting the ribonucleotide reductase R1 subunit. The size distribution of ODN- LNPs was measured by dynamic light scattering. The cytotoxicity of ODN- LNPs was determined by MTS assay. Gene silencing activity of ODN- LNPs was investigated by qRT-PCR and by Western blot. Results showed that MF synthesis produced ODN-LNPs that have lower average size and polydispersity values. The highest antisense activity was shown by LNs synthesized by the MF T2 chip, with downregulation of R1 mRNA by 32.5%. In conclusion, given their simplicity, affordability and reproducibility, MF is an attractive method for synthesis of LNs for ODN delivery.

Keywords: Antisense oligonucleotide, cancer, microfluidics, nanoparticles, ribonucleotide reductase.


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