Posted on 20 May 2016
Cyclodextrins are a class of compounds made up of sugar molecules bound together in a ring (cyclic oligosaccharides). These cone-shaped molecules are hydrophobic inside and hydrophilic outside, meaning that they can form complexes with hydrophobic compounds, encapsulating other molecules within a hydrophobic cavity and hence enhancing the solubility and bioavailability of the encapsulated compounds. These properties make cyclodextrins of great interest to the pharmaceutical and food industries, among others. For example, cyclodextrins are used in the preparation of cholesterol-free products: the bulky and hydrophobic cholesterol molecule is easily lodged inside cyclodextrin rings that are then removed.
Tom’s MChem project, which focused on use of cyclodextrins in drug solubilisation, aimed to tackle the lack of fundamental molecular-level understanding of the overall solubilisation mechanism: traditional views are that the “encapsulation” is the only thing that leads to cyclodextrin's ability to improve solubility; however, some scientists have noticed that there is behaviour (non-linear solubility enhancement) that cannot be described using only the encapsulation/ inclusion approach.
The original idea to study cyclodextrins was Tom’s, and he worked with his project supervisor, Dr Seishi Shimizu, and Seishi’s longstanding collaborator Professor Nobuyuki Matubayasi of Osaka University (both of whom provided input on the complex mathematical derivations required), to shed light on the variety of molecular-level interactions taking place.
Statistical thermodynamic theory shows that solubility is affected by changes in interaction between the cyclodextrin molecules, when the drug or other molecule is introduced, as well as by the interactions between cyclodextrin and the other molecule. Or put in more technical terms, the solubilisation behaviour's deviation from linearity is due to competition between cyclodextrin self-association changes induced by introduction of the drug molecule, and direct drug-cyclodextrin interactions. Understanding the nature of such a subtle and elusive mechanism will help scientists improve solubility and achieve more effective delivery of drug compounds.
Tom described the theoretical work as “both challenging and rewarding; also, it reveals molecular level interactions which are of great interest to me”. He will return to the Department in September to start a PhD project on “Solubilisation of biomass polysaccharides by bio-derived solvent: optimisation and mechanistic studies”, co-supervised by Seishi and Professor James Clark.
“Origin of nonlinearity in phase solubility: Solubilisation by cyclodextrin beyond stoichiometric complexation” Tom W.J. Nicol, Nobuyuki Matubayasi, and Seishi Shimizu, Physical Chemistry Chemical Physics, 2016