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Title: The biophysical effects of nanosized particles in contact with alveolar lung surfactant
Author: Miguel Diez, Maria
ISNI:       0000 0004 8504 3527
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2017
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The effects of engineered nanoparticles (NPs) on the biophysical properties of lung surfactant is a topic of increasing interest due to the rapid expansion of nanotechnologies and the potential for human exposure to airborne NPs. Langmuir monolayers of dipalmitoylphosphatidylcholine (DPPC), the major component of the lung surfactant, at the air/liquid interface represent a good model to investigate the lung surfactant behaviour and its interactions with NPs. Here, the effects of CeO2 and Carbon Black (CB) NPs on DPPC monolayers were investigated by the analysis of surface pressure-Mma (Π-Mma) compression isotherms recorded at experimental conditions similar to those found in human lungs using a Langmuir-Wilhelmy Balance (LWB) in parallel with the visualisation of the interface using SEM and ToF-SIMS. In previous studies, NPs were deposited from liquid suspensions, usually for ease of application. In this work, a method for aerosol NP deposition onto DPPC monolayers was developed and compared with depositions from liquid suspensions. To date, there are no other studies of NP deposition onto a surfactant monolayer in aerosol form using a LWB. CeO2 NPs were first suspended in chloroform and deposited onto a DPPC monolayer located at the air/PBS interface, which had no effect on the Π-Mma isotherm for any of the NP mass deposited due to the instability of CeO2 NPs in this medium which rapidly agglomerated to form large, dense clusters that eventually detached from the interface and sedimented into the subphase hence, only small CeO2 NPs remained at the surface at levels too low to affect the isotherm. In the second deposition method, NPs were mixed with DPPC in chloroform and deposited onto a clean PBS subphase. The coating of the NPs with DPPC increased the stability of the NPs in PBS. SEM and ToF-SIMS images showed that large agglomerates were present at the interface that had a remarkable effect on the Π-Mma isotherms by shifting them towards larger areas with NP mass deposited. Thirdly, CeO2 NPs in aerosol form were deposited onto a DPPC monolayer. Results showed that the presence of agglomerates of a similar size homogeneously spread across the surface during the compression of the interface improved the film containment causing an increase in the slope of the isotherm starting at a Π ~ 30 mN/m and in the collapse Π with NP mass deposited. Aerosolised CB NPs were also distributed uniformly across the surface and improved the stability of the monolayer in a similar way to aerosolised CeO2 NPs. These experiments showed that the NP deposition method onto the air/PBS interface differentially affected the DPPC isotherm and that the degree of NP agglomeration is probably one of the most important determining factors of the NP effects on the DPPC isotherm. It is concluded that the deposition of NPs in aerosol form is the most appropriate experimental model to study inhaled NP interactions with lung surfactant using a LWB.
Supervisor: Tetley, Terry ; Smith, Rachel ; Buckley, Alison Sponsor: Public Health England
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral