Microfluidic assembly of lipid-based oligonucleotide nanoparticles.
Microfluidic assembly of lipid-based oligonucleotide nanoparticles.
复制标题
DOI：
--
复制
发表时间：
2011-03
影响因子：
2
通讯作者：
Bo Yu;Jing Zhu;Weiming Xue;Yun Wu;Xiaomeng Huang;L. J. Lee;Robert J. Lee
中科院分区：
文献类型：
--
作者：
Bo Yu;Jing Zhu;Weiming Xue;Yun Wu;Xiaomeng Huang;L. J. Lee;Robert J. Lee
寡核苷酸（ONs）作为一种治疗多种疾病的药物已显示出巨大的前景。有必要提供一种在实验室规模上可重复的方式制备负载脂质纳米颗粒（LNPs）的方案。材料与方法采用3进路微流控芯片合成LNPs，脂质/ON比为10/1 (w/w)，流速为50 ~ 1100 μl/min。合成了一系列含有反义寡脱氧核糖核苷酸（AS-ODN）或小干扰RNA （siRNA）的LNPs。以散装混合为对照。结果表明，MF法对合成负载AS-ODN的LNPs特别有用。AS-ODN LNPs的最佳流速范围为100 ~ 200 μl/min。MF合成产生的LNPs具有较低的多分散性值。然而，MF在制备装载siRNA的LNPs时效果较差，这可能是由于与单链AS-ODN相比，双链siRNA具有更大的刚性。结论MF技术是一种简便、经济、重复性好的ON-LNPs生产方法。
BACKGROUND Oligonucleotides (ONs) have shown great promise as therapeutic agents for various diseases. It is necessary to provide a protocol for preparation of ON-loaded lipid nanoparticles (LNPs) in a reproducible manner on a laboratory scale. MATERIALS AND METHODS A 3-inlet microfluidic (MF) chip-based device was used to synthesize LNPs at the lipid/ON ratio of 10/1 (w/w) and at flow rates ranging from 50 to 1100 μl/min. A series of LNPs containing either antisense oligodeoxyribonucleotide (AS-ODN) or small-interfering RNA (siRNA) were synthesized. Bulk mixing was used as control. RESULTS The MF method was shown to be particularly useful for synthesis of LNPs loaded with AS-ODN. The optimal range of flow rates for AS-ODN LNPs was found to be 100 to 200 μl/min. MF synthesis produced LNPs with lower polydispersity values. However, the MF was less effective in preparing LNPs loaded with siRNA, which may have been due to greater rigidity of double-stranded siRNA comparing to single-stranded AS-ODN. CONCLUSION MF technology is a simple, affordable and reproducible method for production of ON-LNPs.