eprintid: 10113139 rev_number: 21 eprint_status: archive userid: 608 dir: disk0/10/11/31/39 datestamp: 2020-11-02 12:34:02 lastmod: 2021-09-17 22:26:17 status_changed: 2020-11-02 12:34:02 type: article metadata_visibility: show creators_name: Yanar, F creators_name: Mosayyebi, A creators_name: Nastruzzi, C creators_name: Carugo, D creators_name: Zhang, X title: Continuous-Flow Production of Liposomes with a Millireactor under Varying Fluidic Conditions ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D10 divisions: G08 keywords: continuous-flow production, drug delivery, liposome, millifluidic reactor, solvent exchange note: © 2020 by the Authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). abstract: Continuous-flow production of liposomes using microfluidic reactors has demonstrated advantages compared to batch methods, including greater control over liposome size and size distribution and reduced reliance on post-production processing steps. However, the use of microfluidic technology for the production of nanoscale vesicular systems (such as liposomes) has not been fully translated to industrial scale yet. This may be due to limitations of microfluidic-based reactors, such as low production rates, limited lifetimes, and high manufacturing costs. In this study, we investigated the potential of millimeter-scale flow reactors (or millireactors) with a serpentine-like architecture, as a scalable and cost-effective route to the production of nanoscale liposomes. The effects on liposome size of varying inlet flow rates, lipid type and concentration, storage conditions, and temperature were investigated. Liposome size (i.e., mean diameter) and size dispersity were characterised by dynamic light scattering (DLS); z-potential measurements and TEM imaging were also carried out on selected liposome batches. It was found that the lipid type and concentration, together with the inlet flow settings, had significant effects on the properties of the resultant liposome dispersion. Notably, the millifluidic reactor was able to generate liposomes with size and dispersity ranging from 54 to 272 nm, and from 0.04 to 0.52 respectively, at operating flow rates between 1 and 10 mL/min. Moreover, when compared to a batch ethanol-injection method, the millireactor generated liposomes with a more therapeutically relevant size and size dispersity. date: 2020-11 date_type: published official_url: https://doi.org/10.3390/pharmaceutics12111001 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1823789 doi: 10.3390/pharmaceutics12111001 pii: pharmaceutics12111001 lyricists_name: Carugo, Dario lyricists_id: DCARU23 actors_name: Carugo, Dario actors_id: DCARU23 actors_role: owner full_text_status: public publication: Pharmaceutics volume: 12 number: 11 article_number: 1001 event_location: Switzerland citation: Yanar, F; Mosayyebi, A; Nastruzzi, C; Carugo, D; Zhang, X; (2020) Continuous-Flow Production of Liposomes with a Millireactor under Varying Fluidic Conditions. Pharmaceutics , 12 (11) , Article 1001. 10.3390/pharmaceutics12111001 <https://doi.org/10.3390/pharmaceutics12111001>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10113139/1/pharmaceutics-12-01001-v2.pdf