Understanding the formation mechanism of lipid nanoparticles in microfluidic devices with chaotic micromixers (original) (raw)

Microfluidic approach for production of lipid nanoparticles-based nano medicine

2015

This paper described a simple preparation method for small-size and monodispersed lipid nanoparticles (LNPs) by using microfluidic devices. The fundamental role and importance of chaotic micromixer in the microfluidic device was demonstrated. The suitable cycle number of chaotic micromixer was confirmed for precise controlling LNPs size with narrow distribution under the any flow rate conditions. In addition, LNPs containing siRNA was synthesized for evaluation of penetration efficiency via in vivo experiment. The PEGylated LNPs containing siRNA with a diameter of 30 nm could penetrate to the mouse parenchymal liver cells rather than the LNPs with a diameter of 50 nm.

Optimal Self-assembly of Lipid Nanoparticles (LNP) in a Ring Micromixer

2022

Lipid nanoparticles (LNPs) for RNA and DNA delivery have gained considerable attention to treat a broad range of diseases and to vectorize mRNA for COVID vaccines. LNPs are produced by mixing biomolecules and lipids, which self-assemble to form the desired structure. In this domain, microfluidics shows clear advantages: high mixing quality under low stress conditions added to fast preparation. Studies of LNPs produced in micromixers have revealed, in certain ranges of flow-rates, a degradation of performances in terms of size, size monodispersivity and encapsulation efficiency. In this study we focus on the ring micromixer, well adapted to high throughputs. We reveal three regimes - side-by-side, transitionnal and highly mixed – which control the mixing performance of the device. Further, on using cryo-TEM and biochemical analysis, we show that the mixing performances are strongly correlated to the characteristics of the LNPs we produce. We underline the important role of the flow-r...

High-throughput nanoscale liposome formation via electrohydrodynamic-based micromixer

Physics of Fluids

Liposomes are one of the most attractive particles in different industries, especially pharmaceutical applications. The main reasons for such a desire for liposomes are non-toxicity, small size, the ability to encapsulate and carry biological components, and finally biocompatibility and biodegradability. The present study aims to simulate the active electrohydrodynamic-based micromixer for the high-throughput formation of nanoscale liposomes. The micromixer consists of two inlets for DI water and one inlet for ethanol with lipid particles. Two configurations of asymmetric electrodes namely longitudinal and the array of electrodes were introduced and examined. Electrodes were placed at the bottom of the mixer and a DC electrical field was applied to them. Generated chaotic advection inside the microchannel by the electrical field and consequently increasing surface-to-volume ratio is the main reason for the increase in the formation of liposomes. These configurations of electrodes ca...

The Impact of Solvent Selection: Strategies to Guide the Manufacturing of Liposomes Using Microfluidics

Pharmaceutics, 2019

The aim of this work was to assess the impact of solvent selection on the microfluidic production of liposomes. To achieve this, liposomes were manufactured using small-scale and bench-scale microfluidics systems using three aqueous miscible solvents (methanol, ethanol or isopropanol, alone or in combination). Liposomes composed of different lipid compositions were manufactured using these different solvents and characterised to investigate the influence of solvents on liposome attributes. Our studies demonstrate that solvent selection is a key consideration during the microfluidics manufacturing process, not only when considering lipid solubility but also with regard to the resultant liposome critical quality attributes. In general, reducing the polarity of the solvent (from methanol to isopropanol) increased the liposome particle size without impacting liposome short-term stability or release characteristics. Furthermore, solvent combinations such as methanol/isopropanol mixtures ...