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

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

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: Apr 1, 2023
• Journal: Journal of Controlled Release
• Print ISSN: 0168-3659
• Electronic ISSN: 1873-4995
• Publisher: Elsevier
• 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