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Molecules 2016, 21(10), 1314; doi:10.3390/molecules21101314

Synthesis of Polymer-Lipid Nanoparticles by Microfluidic Focusing for siRNA Delivery

1
School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun 130012, China
2
Department of Chemistry and Pharmacy, Zhuhai College of Jilin University, Zhuhai 519041, China
3
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Daniela Montesarchio
Received: 16 July 2016 / Revised: 13 August 2016 / Accepted: 20 September 2016 / Published: 17 October 2016
(This article belongs to the Special Issue Nucleic Acid-based Drug)
View Full-Text   |   Download PDF [3450 KB, uploaded 17 October 2016]   |  

Abstract

Polyethylenimine (PEI) as a cationic polymer is commonly used as a carrier for gene delivery. PEI-800 is less toxic than PEI-25K but it is also less efficient. A novel nanocarrier was developed by combining PEI-800 with a pH-sensitive lipid to form polymer-lipid hybrid nanoparticles (P/LNPs). They were synthesized by microfluidic focusing (MF). Two microfluidic devices were used to synthesize P/LNPs loaded with VEGF siRNA. A series of P/LNPs with different particle sizes and distributions were obtained by altering the flow rate and geometry of microfluidic chips, and introducing sonication. Furthermore, the P/LNPs can be loaded with VEGF siRNA efficiently and were stable in serum for 12 h. Finally, P/LNPs produced by the microfluidic chip showed greater cellular uptake as well as down-regulation of VEGF protein level in both A549 and MCF-7 with reduced cellular toxicity. All in all, the P/LNPs produced by MF method were shown to be a safe and efficient carrier for VEGF siRNA, with potential application for siRNA therapeutics. View Full-Text
Keywords: microfluidic; polymer; lipid nanoparticles; siRNA microfluidic; polymer; lipid nanoparticles; siRNA
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Li, Y.; Huang, X.; Lee, R.J.; Qi, Y.; Wang, K.; Hao, F.; Zhang, Y.; Lu, J.; Meng, Q.; Li, S.; Xie, J.; Teng, L. Synthesis of Polymer-Lipid Nanoparticles by Microfluidic Focusing for siRNA Delivery. Molecules 2016, 21, 1314.

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