Lipid-based nanoparticle production in Micromixers

V. Nerguizian, R. Salazar
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Abstract

Lipid-based nanoparticles have demonstrated to be a versatile vehicle for drugs, genetic material, and labels. These particles are often made of biocompatible and biodegradable materials, enabling a safe interaction with biological systems. The importance of this type of delivery vehicle has been shown recently, as the two leading vaccines are based on lipid-nanoparticles encapsulating mRNA. Passive micromixers produce lipid nanoparticles in a reproducible and controllable way. However, micromixers suffered at the beginning of low production rate, and complicated designs which were difficult to produce and prone to clogging. In recent years, the exploration of different mixing strategies based on the use of curvilinear paths to induce centripetal forces and vortex formation at high speeds as well as the increase of the microchannel cross-sectional area while keeping laminar flow regimes has led to designs capable of producing lipid-based nanoparticles on an industrial-scale. However, there are still challenges in the field which include the removal or substitution of the organic solvents that still need to be addressed. In this presentation, we introduce a general overview of lipid nanoparticle or liposome production in micromixers, the principles of mixing using curvilinear paths, the key variables controlling lipid-based nanoparticle physicochemical characteristics and approaches that help to substitute toxic solvent residues.
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微混合器中脂基纳米颗粒的生产
以脂质为基础的纳米颗粒已被证明是药物、遗传物质和标签的多功能载体。这些颗粒通常由生物相容性和可生物降解材料制成,能够与生物系统安全相互作用。这种递送载体的重要性最近得到了证实,因为两种主要的疫苗都是基于脂质纳米颗粒封装mRNA。被动微混合器以可重复和可控的方式生产脂质纳米颗粒。然而,微型混合器在初期存在着生产率低、设计复杂、生产困难、易堵塞等问题。近年来,基于使用曲线路径来诱导高速向心力和涡流形成的不同混合策略的探索,以及在保持层流状态的同时增加微通道横截面积,导致了能够在工业规模上生产基于脂质纳米颗粒的设计。然而,该领域仍然存在挑战,包括有机溶剂的去除或替代仍然需要解决。在本次演讲中,我们介绍了微混合器中脂质纳米颗粒或脂质体生产的总体概述,使用曲线路径混合的原理,控制脂质纳米颗粒物理化学特性的关键变量以及有助于替代有毒溶剂残留物的方法。
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