Nonaqueous microemulsions stabilised by soybean phosphatidylcholine:

: formation, properties and applications as fluoride delivery systems

Abstract

Microemulsions are clear, isotropic and thermodynamically stable mixtures of oil, water and one or more amphiphiles - typically a surfactant and a co-surfactant. Owing to their advantageous properties, including ease of preparation, extended shelf-life and modifiable viscosity, microemulsions have attracted interest as potential formulation media and delivery vesicles in a variety of areas. Nonetheless, few commercial food- and drug-grade microemulsions have been developed over the years, mainly due to the need to use high surfactant concentrations and/or cosurfactants to promote microemulsification, which could lead to toxicity and biocompatibility issues.

To address this problem, in this thesis we explored the formation and properties of biocompatible cosurfactant-free nonaqueous microemulsions, in which the naturally occurring food-grade lipid soybean phosphatidylcholine (SPC) is employed as the surfactant, along with a range of generally regarded as safe polar solvents (PS, used instead of water) and non-polar solvents (NPS, oils). Our studies suggest that the influence of the solvents over the phase behaviour, morphology and interfacial properties of SPC-stabilised systems is predominantly guided by their ability to partition within interfacial SPC structures and alter their properties. This ability is,in turn, positively correlated with the amphiphilic moment (AM) of the PS and negatively correlated with the molecular volume (MV) of the NPS, among other solvent properties of lesser importance.

Additionally, to reduce the cost and experimental effort associated with biocompatible microemulsion development, the phase behaviour results together with a range of solvent descriptors were employed in the development of a machine learning model for the reliable prediction of microemulsion formation in SPC-stabilised systems. Among the solvent properties investigated, the PS AM and NPS MV were again identified as the most important predictors of phase behaviour and the resulting random forest model predicted unseen PS/SPC/NPS partial phase diagrams with an accuracy of 91%.

Lastly, the use of SPC-stabilised microemulsions for the delivery of fluoride to enamel lesions was explored. The results suggest that the addition of stannous fluoride to PS/SPC/NPS systems marginally decreases the range of PS-rich microemulsion-forming compositions and increases the size of the corresponding aggregates. The resulting fluoride-containing microemulsions exhibited acceptable dispersion and fluoride release properties inaqueous environments and marginally increased the uptake of fluoride in artificial enamel lesions.

Date of Award	1 Jul 2020
Original language	English
Awarding Institution	King's College London
Supervisor	Cecile Dreiss (Supervisor), Gino Martini (Supervisor) & Timothy Watson (Supervisor)