King’s College London Health Schools Studentships 2015
Division:
PROJECT DETAILS
Title of project
Understanding the interfacial behaviour of bile salts to better engineer lipid emulsions
Supervisor 1
Dr Cécile Dreiss
Supervisor 2
Dr Richard Harvey
Project description (max 500 words)
Background
The intake of dietary fat and its effects on health has become a major focus of our modern
societies. The rate of fat digestion and subsequent absorption is controlled by the ability of lipase
and its co-enzyme co-lipase to bind to fat droplet interfaces, a process controlled and facilitated by
bile salts (BS), bio-surfactants with an unusual planar structure present in the gastrointestinal tract.
This process is not only relevant to the absorption of dietary fat and fat-soluble nutrients but also
that of poorly soluble drugs1. Yet, there is currently no understanding of the impact of emulsion
structure on the digestion and metabolism of dietary lipids. Controlling the digestion of fats is key
to addressing the pressing issue of excess fat intake – linked to the current obesity crisis and related
cardiovascular diseases – but also to control the release and absorption of drugs in lipid-based
formulations1. One proposed approach for regulating fat digestion is through the use of appropriate
emulsifiers, which compete with BS for adsorption at fat droplet interfaces, thus decreasing the
rate of lipolysis.
Objectives & Rationale
A fundamental understanding of the colloidal and interfacial processes governing lipid digestion
and uptake is needed to guide rational design strategies for food and drug formulations. We
propose a multi-disciplinary approach, using a combination of advanced physical techniques, to
build a detailed mechanistic understanding of cyclodextrin-stabilised nanoemulsions. Cyclodextrins
are well-known pharmaceutical excipients and food adjuvants2,3, and a recent European Health
Claim on α-cyclodextrin makes it an acceptable ‘dietary fibre’, with capacity to lower postprandial
glycaemic and cholesterol levels4. There is however no mechanistic understanding to substantiate
this claim, nor any understanding why related β- and J- cyclodextrins would not achieve the same
effect. The pioneering use of neutron scattering in this area, combined to interfacial techniques and
atomistic computer simulations (Dr Chris Lorenz, Physics), will enable us to better understand
these complex multi-component systems, both in the bulk and at interfaces, at equilibrium and
over time, in systems mimicking physiological fluids.
Work plan
WP1. BS present a rich architectural diversity, which may be a clue to their multifaceted role. WP1
will aim at elucidating the structure/activity relationship in BS. WP2. Microfluidic manufacture of
monodisperse emulsions with a range of selected cyclodextrins (collaboration with Dr J. Cabral,
Imperial College). WP3. Examine interaction of BS with emulsified layers and structures formed
during simulated digestion, in bulk systems and at interfaces. WP4. Determine in vitro lipid and
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drug release during simulated digestion. WP5. Correlate changes in lipolysis to BS and cyclodextrin
structure, stabilising layers characteristics and self-assembled structures.
Conclusions. The project addresses fundamental scientific questions and very timely practical
challenges, promising results of particular relevance to both the food and pharmaceutical
industries.
References.
[1] Porter et al. Nat. Rev. (2007) 6, 231-248 [2] Davis & Brewster Nat. Rev. (2004) 3, 1023-1035 [3]
Szente & Szejtli Trends Food Sci Technol. (2004) 15, 137-142 [4] European Food Safety Authority
(EFSA), ID 856, 2926, 2925 [5] Parker et al. Soft Matter (2014) 10, 6457-6466
Please indicate the type of programme
4 years
1+ 3 years (lab rotations)
MRes + 3 years
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