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Loop configuration for continuous antisolvent precipitation of lipid nanoparticles
Date
2026-05-01
Abstract
Continuous antisolvent precipitation has emerged as a scalable method for producing lipid nanoparticles (LNPs). Devices used for conducting antisolvent precipitation of LNPs are typically used in a once-through configuration. In such a once-through configuration, either high flow rates need to be used (for meso-scale devices like impinging jet mixers) or microfluidic devices need to be used. Another important drawback of once through configuration is that the size of produced LNPs increases with increase in inlet lipid concentration and therefore low lipid concentrations are typically used, leading to undesirably low concentration of LNPs in the product stream. In this work, we demonstrate synthesis of highly concentrated LNP suspensions (up to 50 mg/mL) using a loop configuration without jeopardising the limits on size and polydispersity index (PDI). A coiled pinched tube, a fluidic device with no moving parts, was used for continuous antisolvent precipitation of LNPs composed of Imwitor 742 lipid. The loop configuration decouples achievable micro-mixing time from the net throughput. The size and PDI were maintained despite an order of magnitude increase in lipid concentration, and thereby greatly simplifying downstream handling and improving overall process efficiency. The approach provides a robust and scalable route toward continuous manufacturing of lipid-based therapeutic formulations.
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Description
Publisher
Elsevier
Citation
Chemical Engineering Journal Advances 26, 101136
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Joshi_2026_Loop.pdf
Adobe PDF, 1.61 MB
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Funding Information
Sustainable Development Goals
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License
Attribution-NonCommercial-ShareAlike 4.0 International