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Lipid Nanoparticles: Microfluidics & Artificial Intelligence – K. Alhareth

The vector team conceive and synthesize novel lipids for mRNA delivery and optimise their formulations.

The team has pionnered mRNA Post-encapsulation methologies for

Nathalie Mignet has been funded for a LabCO with the company Neovacs and is leading the program VECT-PI to pursue her research on lipids with endosomal release capacities.

Nanoparticle preparation by microfluidics is proving to be a crucial approach thanks to the high reproducibility of production and the control of synthesis parameters. The microfluidic technique also allows producing nanoparticles at different scales, with production volume ranging from a few hundred microliters to several tens of liters, depending on the equipment.

At UTCBS, we use microfluidics for the development, preparation, and functionalization of liposomes. Different production parameters and conditions have been studied: lipid composition, molar ratio, concentration, flow conditions and chip geometry.

The development of this approach for nanoparticles preparation by advanced and automatable technologies, such as microfluidics, is in perfect synergy with the application of artificial intelligence (AI) tools. In this project, the complexity, quantity and quality of data encourage i) the use of design of experiments (DoE) to design series of tests, ii) the automation of data collection, transformation and visualization, iii) and the development of models based on artificial neural networks (ANN) to predict nanoparticle physicochemical properties.

Microfluidics and AI – assisted preparation methods allowed to optimize the formulation and the production of liposomes and would certainly accelerate the development and clinical transfer of nanoparticle-based drugs.

Duffrène, C. Muzard, J. Seguin, C. Izabelle, T. Vrai, T. Ejlalmanesh, M. Bombled, S. Hamdi, K. Lemdani, K. Alhareth and N. Mignet. Post-encapsulation methods for the preparation of mRNA-LNPs. Drug Deliv Transl Res. 2025, hal-05705116v1

Microfluidic liposome manufacturing: Development and optimization using experimental design and machine learning

• Rebollo R, Oyoun F, Corvis Y, El-Hammadi MM, Saubamea B, Andrieux K, Mignet N, Alhareth K. Microfluidic Manufacturing of Liposomes: Development and Optimization by Design of Experiment and Machine Learning. ACS Appl Mater Interfaces. 2022 Sep 7;14(35):39736-39745. doi: 10.1021/acsami.2c06627.
• Huiyu Chen and Khair Alhareth, « Optimization of the ethanol removal step of liposome production using microfluidics. », Oral presentation, the 6th EMJMD NANOMED WORKSHOP, Rio-Patras, Greece, July 2023.
• Georgia Hanley, Pauline Chavrier, Mattia Tiboni, Luca Casettari, Khair Alhareth, Karine Andrieux, « From thin-film hydration to microfluidics: a translational approach for the preparation of liposomes functionalized with a peptide isolated from VAR2CSA for placenta targeting. », Poster, the 6th EMJMD NANOMED WORKSHOP, Rio-Patras, Greece, July 2023.

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