High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization

Elisabeth Kastner, Randip Kaur, Deborah Lowry, Behfar Moghaddam, Alexander Wilkinson, Yvonne Perrie

Research output: Contribution to journalArticle

Abstract

Microfluidics has recently emerged as a new method of manufacturing liposomes, which allows for reproducible mixing in miliseconds on the nanoliter scale. Here we investigate microfluidics-based manufacturing of liposomes. The aim of these studies was to assess the parameters in a microfluidic process by varying the total flow rate (TFR) and the flow rate ratio (FRR) of the solvent and aqueous phases. Design of experiment and multivariate data analysis were used for increased process understanding and development of predictive and correlative models. High FRR lead to the bottom-up synthesis of liposomes, with a strong correlation with vesicle size, demonstrating the ability to in-process control liposomes size; the resulting liposome size correlated with the FRR in the microfluidics process, with liposomes of 50 nm being reproducibly manufactured. Furthermore, we demonstrate the potential of a high throughput manufacturing of liposomes using microfluidics with a four-fold increase in the volumetric flow rate, maintaining liposome characteristics. The efficacy of these liposomes was demonstrated in transfection studies and was modelled using predictive modeling. Mathematical modelling identified FRR as the key variable in the microfluidic process, with the highest impact on liposome size, polydispersity and transfection efficiency. This study demonstrates microfluidics as a robust and high-throughput method for the scalable and highly reproducible manufacture of size-controlled liposomes. Furthermore, the application of statistically based process control increases understanding and allows for the generation of a design-space for controlled particle characteristics.
LanguageEnglish
Pages361-368
Number of pages8
JournalInternational Journal of Pharmaceutics
Volume477
Issue number1-2
Early online date14 Oct 2014
DOIs
Publication statusPublished - 30 Dec 2014

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Microfluidics
Liposomes
Transfection
Multivariate Analysis

Bibliographical note

© 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Funding: EPSRC; NewTBVAC (contract no. HEALTHF3-2009-241745)and Aston University

Supplementary data at http://dx.doi.org/10.1016/j.ijpharm.2014.10.030

Keywords

  • design of experiment
  • DNA delivery
  • high-throughput manufacturing
  • liposomes
  • microfluidics

Cite this

Kastner, Elisabeth ; Kaur, Randip ; Lowry, Deborah ; Moghaddam, Behfar ; Wilkinson, Alexander ; Perrie, Yvonne. / High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization. In: International Journal of Pharmaceutics. 2014 ; Vol. 477, No. 1-2. pp. 361-368.
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High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization. / Kastner, Elisabeth; Kaur, Randip; Lowry, Deborah; Moghaddam, Behfar; Wilkinson, Alexander; Perrie, Yvonne.

In: International Journal of Pharmaceutics, Vol. 477, No. 1-2, 30.12.2014, p. 361-368.

Research output: Contribution to journalArticle

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