Scientific Publications

Journal of Drug Delivery Science and Technology , 87 (2023), 104804

Authors : Martino M., Mouahid A., Sergent M., Desgrouas C., Badens C., Badens E.

A continuous supercritical CO₂ millifluidic process was developed for the preparation of nanoliposomes dedicated to siRNA encapsulation. The process enables the production of narrowly distributed nanoliposomes (≈125–150 nm) with controlled size and high reproducibility, while minimizing the use of organic solvents.

Operating parameters (pressure, temperature, phospholipid concentration) were systematically optimized, identifying phospholipid mass ratio as the key driver of particle size. siRNAs targeting the LMNA gene were successfully encapsulated, and ex-vivo assays demonstrated effective gene silencing with reduced cellular toxicity compared to commercial transfection agents.

This work demonstrates the relevance of supercritical CO₂ millifluidic technologies for scalable, clean and GMP-compatible formulation of nucleic-acid-based drug delivery systems, with potential applications in rare diseases such as progeria.

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20th European Meeting on Supercritical Fluids (EMSF), Maribor, Slovenia, May 26–29, 2024.

A. Mouahid, C. Girard , E. Badens - *Corresponding author: adil.mouahid@univ-amu.fr

AbstractSupercritical fluid technology applied to the elaboration of lipid-based formulations, especially liposomes, has been quite widely described in the literature over the last three decades. Many advantages of using supercritical carbon dioxide for liposome formation are often highlighted such as size control, stability enhancement and mitigation of organic solvent use. The main recent challenges in this field are the size reduction since vesicles smaller than 100 nm allow for a higher rate of cell internalization. Another point of attention, whatever the application field, is the development of less energy intensive processes, consuming less raw materials and solvents. The present study addresses all the different challenges mentioned above. A millifluidic process enabling fluid, equipment and energy savings has been applied to the formation of nanoliposomes. This process, previously applied to the encapsulation of small interfering RNA for gene therapy applications,  has been used in this work for the elaboration of pegylated nanoliposomes encapsulating docetaxel, an anti- cancer drug used for the treatment of different types of cancer.

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