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Continuous‐flow production of liposomes with a millireactor under varying fluidic conditions

Continuous‐flow production of liposomes with a millireactor under varying fluidic conditions
Continuous‐flow production of liposomes with a millireactor under varying fluidic conditions

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.

Continuous‐flow production, Drug delivery, Liposome, Millifluidic reactor, Solvent exchange
1999-4923
1-21
Yanar, Fatih
528029cd-ac53-433f-9908-92a18cae84e5
Mosayyebi, Ali
ab9cf6da-58c4-4441-993b-7d03d5d3549a
Nastruzzi, Claudio
fa760f44-1546-4aa2-838d-242a908ea463
Carugo, Dario
0a4be6cd-e309-4ed8-a620-20256ce01179
Zhang, Xunli
d7cf1181-3276-4da1-9150-e212b333abb1
Yanar, Fatih
528029cd-ac53-433f-9908-92a18cae84e5
Mosayyebi, Ali
ab9cf6da-58c4-4441-993b-7d03d5d3549a
Nastruzzi, Claudio
fa760f44-1546-4aa2-838d-242a908ea463
Carugo, Dario
0a4be6cd-e309-4ed8-a620-20256ce01179
Zhang, Xunli
d7cf1181-3276-4da1-9150-e212b333abb1

Yanar, Fatih, Mosayyebi, Ali, Nastruzzi, Claudio, Carugo, Dario and Zhang, Xunli (2020) Continuous‐flow production of liposomes with a millireactor under varying fluidic conditions. Pharmaceutics, 12 (11), 1-21, [1001]. (doi:10.3390/pharmaceutics12111001).

Record type: Article

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.

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Production_of_Liposomes_with_a_Millireactor_Pharmaceutics_Yanar2020 - Version of Record
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More information

Accepted/In Press date: 19 October 2020
e-pub ahead of print date: 22 October 2020
Published date: November 2020
Keywords: Continuous‐flow production, Drug delivery, Liposome, Millifluidic reactor, Solvent exchange

Identifiers

Local EPrints ID: 445822
URI: http://eprints.soton.ac.uk/id/eprint/445822
ISSN: 1999-4923
PURE UUID: c58435be-d5aa-441a-8495-f3975aae1a80
ORCID for Xunli Zhang: ORCID iD orcid.org/0000-0002-4375-1571

Catalogue record

Date deposited: 08 Jan 2021 17:31
Last modified: 26 Nov 2021 02:52

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Contributors

Author: Fatih Yanar
Author: Ali Mosayyebi
Author: Claudio Nastruzzi
Author: Dario Carugo
Author: Xunli Zhang ORCID iD

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