Rapid Production of Nanoscale Liposomes Using a 3D-Printed Reactor-In-A-Centrifuge: Formulation, Characterisation, and Super-Resolution Imaging
Nanoscale liposomes have been extensively researched and employed clinically for the delivery of biologically active compounds, including chemotherapy drugs and vaccines, offering improved pharmacokinetic behaviour and therapeutic outcomes. Traditional laboratory-scale production methods often suffe...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Micromachines |
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| Online Access: | https://www.mdpi.com/2072-666X/14/9/1763 |
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| author | Yongqing He Davide De Grandi Stanley Chandradoss Gareth LuTheryn Gianluca Cidonio Ricardo Nunes Bastos Valerio Pereno Dario Carugo |
| author_facet | Yongqing He Davide De Grandi Stanley Chandradoss Gareth LuTheryn Gianluca Cidonio Ricardo Nunes Bastos Valerio Pereno Dario Carugo |
| author_sort | Yongqing He |
| collection | DOAJ |
| description | Nanoscale liposomes have been extensively researched and employed clinically for the delivery of biologically active compounds, including chemotherapy drugs and vaccines, offering improved pharmacokinetic behaviour and therapeutic outcomes. Traditional laboratory-scale production methods often suffer from limited control over liposome properties (e.g., size and lamellarity) and rely on laborious multistep procedures, which may limit pre-clinical research developments and innovation in this area. The widespread adoption of alternative, more controllable microfluidic-based methods is often hindered by complexities and costs associated with device manufacturing and operation, as well as the short device lifetime and the relatively low liposome production rates in some cases. In this study, we demonstrated the production of liposomes comprising therapeutically relevant lipid formulations, using a cost-effective 3D-printed reactor-in-a-centrifuge (RIAC) device. By adjusting formulation- and production-related parameters, including the concentration of polyethylene glycol (PEG), temperature, centrifugation time and speed, and lipid concentration, the mean size of the produced liposomes could be tuned in the range of 140 to 200 nm. By combining selected experimental parameters, the method was capable of producing liposomes with a therapeutically relevant mean size of ~174 nm with narrow size distribution (polydispersity index, PDI ~0.1) at a production rate of >8 mg/min. The flow-through method proposed in this study has potential to become an effective and versatile laboratory-scale approach to simplify the synthesis of therapeutic liposomal formulations. |
| first_indexed | 2024-03-10T22:27:14Z |
| format | Article |
| id | doaj.art-99a77a5dd3c742dca67c7e2ab80ea9f4 |
| institution | Directory Open Access Journal |
| issn | 2072-666X |
| language | English |
| last_indexed | 2024-03-10T22:27:14Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Micromachines |
| spelling | doaj.art-99a77a5dd3c742dca67c7e2ab80ea9f42023-11-19T12:00:18ZengMDPI AGMicromachines2072-666X2023-09-01149176310.3390/mi14091763Rapid Production of Nanoscale Liposomes Using a 3D-Printed Reactor-In-A-Centrifuge: Formulation, Characterisation, and Super-Resolution ImagingYongqing He0Davide De Grandi1Stanley Chandradoss2Gareth LuTheryn3Gianluca Cidonio4Ricardo Nunes Bastos5Valerio Pereno6Dario Carugo7Department of Pharmaceutics, School of Pharmacy, University College London, London WC1N 1AX, UKInstitute of Biomedical Engineering (IBME), Department of Engineering Science, University of Oxford, Parks Road, Oxford OX1 3PJ, UKOxford Nanoimaging Limited (ONI), Oxford OX2 8TA, UKNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), The Botnar Research Centre, University of Oxford, Windmill Road, Oxford OX3 7HE, UK3D Microfluidic Biofabrication Laboratory, Center for Life Nano- & Neuro-Science—CLN2S, Italian Institute of Technology (IIT), 00161 Rome, ItalyOxford Nanoimaging Limited (ONI), Oxford OX2 8TA, UKOxford Nanoimaging Limited (ONI), Oxford OX2 8TA, UKDepartment of Pharmaceutics, School of Pharmacy, University College London, London WC1N 1AX, UKNanoscale liposomes have been extensively researched and employed clinically for the delivery of biologically active compounds, including chemotherapy drugs and vaccines, offering improved pharmacokinetic behaviour and therapeutic outcomes. Traditional laboratory-scale production methods often suffer from limited control over liposome properties (e.g., size and lamellarity) and rely on laborious multistep procedures, which may limit pre-clinical research developments and innovation in this area. The widespread adoption of alternative, more controllable microfluidic-based methods is often hindered by complexities and costs associated with device manufacturing and operation, as well as the short device lifetime and the relatively low liposome production rates in some cases. In this study, we demonstrated the production of liposomes comprising therapeutically relevant lipid formulations, using a cost-effective 3D-printed reactor-in-a-centrifuge (RIAC) device. By adjusting formulation- and production-related parameters, including the concentration of polyethylene glycol (PEG), temperature, centrifugation time and speed, and lipid concentration, the mean size of the produced liposomes could be tuned in the range of 140 to 200 nm. By combining selected experimental parameters, the method was capable of producing liposomes with a therapeutically relevant mean size of ~174 nm with narrow size distribution (polydispersity index, PDI ~0.1) at a production rate of >8 mg/min. The flow-through method proposed in this study has potential to become an effective and versatile laboratory-scale approach to simplify the synthesis of therapeutic liposomal formulations.https://www.mdpi.com/2072-666X/14/9/1763liposomesolvent exchangecentrifugal flowmicrofluidicssuper-resolution microscopy |
| spellingShingle | Yongqing He Davide De Grandi Stanley Chandradoss Gareth LuTheryn Gianluca Cidonio Ricardo Nunes Bastos Valerio Pereno Dario Carugo Rapid Production of Nanoscale Liposomes Using a 3D-Printed Reactor-In-A-Centrifuge: Formulation, Characterisation, and Super-Resolution Imaging Micromachines liposome solvent exchange centrifugal flow microfluidics super-resolution microscopy |
| title | Rapid Production of Nanoscale Liposomes Using a 3D-Printed Reactor-In-A-Centrifuge: Formulation, Characterisation, and Super-Resolution Imaging |
| title_full | Rapid Production of Nanoscale Liposomes Using a 3D-Printed Reactor-In-A-Centrifuge: Formulation, Characterisation, and Super-Resolution Imaging |
| title_fullStr | Rapid Production of Nanoscale Liposomes Using a 3D-Printed Reactor-In-A-Centrifuge: Formulation, Characterisation, and Super-Resolution Imaging |
| title_full_unstemmed | Rapid Production of Nanoscale Liposomes Using a 3D-Printed Reactor-In-A-Centrifuge: Formulation, Characterisation, and Super-Resolution Imaging |
| title_short | Rapid Production of Nanoscale Liposomes Using a 3D-Printed Reactor-In-A-Centrifuge: Formulation, Characterisation, and Super-Resolution Imaging |
| title_sort | rapid production of nanoscale liposomes using a 3d printed reactor in a centrifuge formulation characterisation and super resolution imaging |
| topic | liposome solvent exchange centrifugal flow microfluidics super-resolution microscopy |
| url | https://www.mdpi.com/2072-666X/14/9/1763 |
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