Microfluidic Assembly of Lipid Nanoparticles for Delivery of Antisense Oligonucleotides

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

Journal Name: Current Pharmaceutical Biotechnology

Volume 15 , Issue 9 , 2014

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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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Article Details

VOLUME: 15
ISSUE: 9
Year: 2014
Page: [823 - 828]
Pages: 6
DOI: 10.2174/1389201015666141020155417
Price: $58

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