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Enhanced permeation by amphiphilic surfactant is spatially heterogenous at membrane and cell level

Cavanagh, Robert; Shubber, Saif; Vllasaliu, Driton; Stolnik, Snjezana

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Authors

Saif Shubber

Driton Vllasaliu

Snjezana Stolnik



Abstract

In the context of increased interest in permeability enhancement technologies to achieve mucosal delivery of drugs and biologics, we report our study on effects of the amphiphilic surfactant at cell membrane and cell population levels. Our results show that modulation in membrane order and fluidity initially occurs on insertion of individual surfactant molecules into the outer leaflet of membrane lipid bilayer; a process occurring at concentrations below surfactant's critical micellar concentration. The surfactant insertion, and consequent increase in membrane fluidity, are observed to be spatially heterogenous, i.e. manifested as ‘patches’ of increased membrane fluidity. At the cell population level, spatially heterogeneous activity of surfactant is also manifested, with certain cells displaying high permeability amongst a ‘background’ population. We propose that this heterogeneity is further manifested in a broad profile of intracellular and nuclear exposure levels to a model drug (doxorubicin) observed in cell population. The study points to heterogeneous nature of surfactant effects at cell membrane and cells in population levels.

Citation

Cavanagh, R., Shubber, S., Vllasaliu, D., & Stolnik, S. (2022). Enhanced permeation by amphiphilic surfactant is spatially heterogenous at membrane and cell level. Journal of Controlled Release, 345, 734-743. https://doi.org/10.1016/j.jconrel.2022.03.053

Journal Article Type Article
Acceptance Date Mar 27, 2022
Online Publication Date Mar 31, 2022
Publication Date May 1, 2022
Deposit Date Apr 27, 2022
Publicly Available Date Mar 29, 2024
Journal Journal of Controlled Release
Print ISSN 0168-3659
Electronic ISSN 1873-4995
Publisher Elsevier BV
Peer Reviewed Peer Reviewed
Volume 345
Pages 734-743
DOI https://doi.org/10.1016/j.jconrel.2022.03.053
Keywords Pharmaceutical Science
Public URL https://nottingham-repository.worktribe.com/output/7834795
Publisher URL https://www-sciencedirect-com.nottingham.idm.oclc.org/science/article/pii/S0168365922001870?via%3Dihub

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