Cyclodextrins are cyclic oligosaccharides consisting of ct(1,4)-linked D-glucopyranosyl units. These macrocycles possess a hydrophobic cavity which can encapsulate molecules such as drugs, and can be chemically modified with relative ease. We propose to develop a range of novel water-soluble amphiphilic and dendrimeric cyclodextrins, which can potentially form different types of molecular assemblies, such as monolayers, nanospheres, polar heterodimers, micelles and liposomes. The most interesting possibility raised by these self-assembling host molecules is the formation of host-guest complexes within the supramolecular assemblies, applied to drug-delivery.These properties will be assessed by physico-chemical methods.
Liquid crystalline properties will be investigated by DSC and X-ray diffraction. Micellisation (effects of structure, solvent) will be measured by light scattering and fluorescent probes. Liposome formation will be sought using electron microscopy and atomic force microscopy. Polar heterodimer formation between charged cyclodextrins will be measured by potentiometric titrations.
The supramolecular assemblies confirmed above will be applied to inclusion of guests: inclusion of phosphonucleotides by cationic compounds will be studied by potentiometry; inclusion of fluorescent probes by micellar and liposomal systems will be followed by fluorescence spectroscopy; inclusion of peptide drugs such as Somatuline (Biomeasure Inc.) will be evaluated by NMR and UV spectroscopies.
Training content (objective, benefit and expected impact)
The Dublin Project will enable me to extend my experience of metal complexation to the complementary area of organic guest molecules complexes. It will widen my knowledge of physico-chemical methods and give me an interdisciplinary experience, which will benefit my employment prospects in pharmaceutical research.
Links with industry / industrial relevance (22)
The project has the expressed interest of: (1) Kinerton Ltd (U.S. parent Co. Biomeasure Inc.) for peptide drug delivery; (2) Elan Ltd., an internationally known drug-delivery company.