High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization
Kastner, Elisabeth and Kaur, Randip and Lowry, Deborah and Moghaddam, Behfar and Wilkinson, Alexander and Perrie, Yvonne (2014) High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization. International Journal of Pharmaceutics, 477 (1-2). pp. 361-368. ISSN 1873-3476 (https://doi.org/10.1016/j.ijpharm.2014.10.030)
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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.
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Item type: Article ID code: 56827 Dates: DateEvent30 December 2014Published14 October 2014Published Online11 October 2014AcceptedNotes: Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved. Subjects: Medicine > Therapeutics. Pharmacology Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Depositing user: Pure Administrator Date deposited: 05 Jul 2016 00:04 Last modified: 07 Oct 2024 07:26 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/56827