Journal
JOURNAL OF CONTROLLED RELEASE
Volume 345, Issue -, Pages 734-743Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2022.03.053
Keywords
Permeability enhancement; Amphiphilic surfactant; Non-ionic surfactant; Liposomes
Funding
- BBSRC [BB/H016538/1]
- MRC [1872576]
- BBSRC [BB/H016538/1] Funding Source: UKRI
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In the context of increased interest in permeability enhancement technologies, this study investigates the effects of an amphiphilic surfactant on cell membrane and cell population levels. The results show that the surfactant can modulate membrane order and fluidity, and its activity is spatially heterogeneous. It also affects the permeability of certain cells within a population.
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 con-centrations 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 het-erogeneity 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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