College of Pharmacy, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada.
Children Hospital's Research Institute of Manitoba, Winnipeg, Manitoba R3E 3P4, Canada.
ACS Appl Bio Mater. 2023 Sep 18;6(9):3566-3576. doi: 10.1021/acsabm.1c00732. Epub 2021 Sep 8.
Nucleic acid therapeutics hold an unprecedented promise toward treating many challenging diseases; however, their use is hampered by delivery issues. Microfluidics, dealing with fluids in the microscale dimensions, have provided a robust means to screening raw materials for development of nano delivery vectors, in addition to controlling their size and minimizing their polydispersity. In this mini-review, we are briefly highlighting the different types of nucleic acid therapies with emphasis on the delivery requirement for each type. We provide a thorough review of available methods for the development of nanoparticles, especially lipid nanoparticles (LNPs) that resulted in FDA approval of the first ever nucleic acid nanomedicine. We then focus on recent research attempts for how microfluidic synthesis of lipid nanoparticles and discuss the various parameters required for successful formulation of LPNs including chip design, flow regimes, and lipid composition. We then identify key areas of research in microfluidics and related fields that require attention for future success in clinical translation of nucleic acid nanomedicines.
核酸疗法在治疗许多挑战性疾病方面具有前所未有的前景；然而，它们的应用受到了传递问题的阻碍。微流控技术在微尺度范围内处理流体，为筛选纳米递药载体的开发原材料提供了一种强大的手段，此外还可以控制其大小并最小化其多分散性。在这篇迷你综述中，我们简要介绍了不同类型的核酸疗法，重点介绍了每种类型的递药要求。我们全面回顾了可用于开发纳米颗粒的方法，特别是脂质纳米颗粒 (LNP)，这些方法促成了首个核酸纳米药物获得 FDA 批准。然后，我们专注于脂质纳米颗粒的微流体制备的最新研究尝试，并讨论了成功配制 LPN 所需的各种参数，包括芯片设计、流动状态和脂质组成。然后，我们确定了微流控技术及相关领域需要关注的关键研究领域，以便未来在核酸纳米药物的临床转化中取得成功。
