Surfactant-Mediated Assembly of Precision-Size Liposomes
Name
pires-et-al-2024-surfactant-mediated-assembly-of-precision-size-liposomes.pdf
Description
Published version
Size
8.57 MB
Format
Adobe PDF
Checksum (MD5)
7296793f69a1edf9cc72df1567880714
Author(s)
Pires, Ivan S
Suggs, Jack R
Carlo, Isabella S
Yun, DongSoo
Hammond, Paula T
Irvine, Darrell J
Date Issued
August 13, 2024
Journal
Chemistry of Materials
Publisher
American Chemical Society
Citation
Ivan S. Pires, Jack R. Suggs, Isabella S. Carlo, DongSoo Yun, Paula T. Hammond, and Darrell J. Irvine. Chemistry of Materials 2024 36 (15), 7263-7273.
Version
Final published version
Abstract
Liposomes can greatly improve the pharmacokinetics of therapeutic agents due to their ability to encapsulate drugs and accumulate in target tissues. Considerable effort has been focused on methods to synthesize these nanocarriers in the past decades. However, most methods fail to controllably generate lipid vesicles at specific sizes and with low polydispersity, especially via scalable approaches suitable for clinical product manufacturing. Here, we report a surfactant-assisted liposome assembly method enabling the precise production of monodisperse liposomes with diameters ranging from 50 nm to 1 μm. To overcome scalability limitations, we used tangential flow filtration, a scalable size-based separation technique, to readily concentrate and purify the liposomal samples from more than 99.9% of detergent. Further, we propose two modes of liposome self-assembly following detergent dilution to explain the wide range of liposome size control, one in which phase separation into lipid-rich and detergent-rich phases drives the formation of large bilayer liposomes and a second where the rate of detergent monomer partitioning into solution controls bilayer leaflet imbalances that promote fusion into larger vesicles. We demonstrate the utility of controlled size assembly of liposomes by evaluating nanoparticle uptake in macrophages, where we observe a clear linear relationship between vesicle size and total nanoparticle uptake.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1021/acs.chemmater.4c01127
