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.
Current Pharmaceutical Biotechnology
Title:Microfluidic Assembly of Lipid Nanoparticles for Delivery of Antisense Oligonucleotides
Volume: 15 Issue: 9
Author(s): Yulin Zhou, Zhaoli Meng, Tianqi Guo, Yige Fu, Robert J. Lee and Jing Xie
Affiliation:
Keywords: Antisense oligonucleotide, cancer, microfluidics, nanoparticles, ribonucleotide reductase.
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.
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Cite this article as:
Zhou Yulin, Meng Zhaoli, Guo Tianqi, Fu Yige, Lee J. Robert and Xie Jing, Microfluidic Assembly of Lipid Nanoparticles for Delivery of Antisense Oligonucleotides, Current Pharmaceutical Biotechnology 2014; 15 (9) . https://dx.doi.org/10.2174/1389201015666141020155417
DOI https://dx.doi.org/10.2174/1389201015666141020155417 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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