Surfactant aggregate structures in bulk solutions have maintained their crucial importance in science and technology as they have a wide range of applications in a plethora of different industries. Surfactant molecules consist of polar head groups and nonpolar tails. Because of this chemical composition, surfactant molecules spontaneously self-assemble into aggregate structures when their concentration in water exceeds their critical micelle concentration. This thesis focusses specifically on the interaction of drug molecules within surfactant monolayers and micelles. The hydrophobic microenvironment arising from the resulting aggregate structures can be used to enhance the solubility of other, partially soluble substances by a process referred to in the literature as “solubilisation”. The encapsulation of these poorly water soluble drug compounds, within surfactant micelles, enables their oral delivery to patients. Sodium dodecyl sulphate micelles show great promise as drug delivery vehicles for hydrophobic compounds in general and the purpose of this thesis is to develop an understanding of how the molecular components of a micellar drug delivery system affect the observed encapsulation ability. Using a combination of atomistic molecular dynamics and well-tempered metadynamics simulations, the interaction of testosterone-based compounds within dodecyl sulphate monolayers and micelles with different counterions has been investigated in detail. In addition, the resulting effects on the structural and interfacial properties of these aggregate structures is investigated thoroughly. The results presented within this thesis show that ammonium ions compete with water molecules to form hydrogen bonds with the dodecyl sulphate headgroups. In doing so, they result in distinctly different interfacial properties of dodecyl sulphate monolayers compared to those with sodium ions, including the dehydration of the surfactant headgroups. This provides a possible explanation for the recently discovered experimental observation that SDS micelles encapsulate significantly more testosterone-based compounds than ADS micelles, despite the micelles being similar in size. Furthermore, the simulation results reported within this thesis reveal that the orientational behaviour of testosterone-based compounds varies depending on the number of polar interaction sites contained within each molecule. This is an effect which could have profound implications of the encapsulation behaviour of the drug compounds studied. The testosterone-based compounds are used as model drug molecules within the framework of this thesis, however the results obtained will aid the rationale design of new oral medications in the future. Moreover, the novel methods which have ben developed to construct an intrinsic surface of planar and (approximately) spherical interfaces of soft matter have significant scope for application in understanding the interfacial properties of these systems as studied within simulations and also as a collective variable when carrying out enhanced sampling simulations using techniques such as metadynamics.
|Date of Award
|1 Sept 2017
|Chris Lorenz (Supervisor) & Carla Molteni (Supervisor)