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

Research output: Contribution to journalArticlepeer-review

Robert Cavanagh, Saif Shubber, Driton Vllasaliu, Snjezana Stolnik

Original languageEnglish
Pages (from-to)734-743
Number of pages10
JournalJournal of Controlled Release
Volume345
Early online date6 Apr 2022
DOIs
Accepted/In press27 Mar 2022
E-pub ahead of print6 Apr 2022
PublishedMay 2022

Bibliographical note

Funding Information: The authors acknowledge funding obtained from BBSRC Grant BB/H016538/1 and MRC Grant 1872576 . Publisher Copyright: © 2022

King's Authors

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.

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