Scalable solvent-free production of liposomes

Khadke, Swapnil and Roces, Carla B. and Donaghey, Rachel and Giacobbo, Valeria and Su, Yang and Perrie, Yvonne (2020) Scalable solvent-free production of liposomes. Journal of Pharmacy and Pharmacology, 72 (10). pp. 1328-1340. ISSN 0022-3573 (

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Objectives. A major challenge faced with the manufacture of liposomes is the high volumes of organic solvents used and disposed of during manufacturing. Therefore, we have implemented an organic solvent-free production method for drug-loaded liposomes and demonstrated its applicability with both aqueous core loaded and bilayer loaded drugs. Methods. Liposomes were produced by high-shear mixing dry powder lipids with an aqueous buffer, followed by down-sizing using a Microfluidizer® processor. Liposomes were purified via tangential flow filtration and characterised in terms of size, polydispersity, zeta potential and drug loading. Key findings. Doxorubicin-loaded PEGylated liposomes can be manufactured using this solvent-free method with particle sizes of 100-110 nm, low PDI (<0.2) and high drug loading (97 - 98%). If required, liposomes can be further down-sized via further microfluidic processing without impacting drug loading. Similar results were achieved with non-PEGylated liposomes. With bilayer loaded amphotericin B liposomes, again liposomes can be prepared within a clinically appropriate size range (100 – 110 nm in size, low PDI) with high drug loading (98 - 100 %). Conclusions. We apply a simple and scalable solvent-free method for the production of both aqueous core or bilayer drug loaded liposomes.