M. Guardo

Physico-chemical characterization of an amphiphilic cyclodextrin/genistein complex.

Specific recognition of cell-targeting systems as host-carriers modified with receptor targeting groups, is a major ambition in the application of supramolecular science to medicine and life science. Genistein (Gen), an isoflavone belonging to the class of phytoestrogens, is of great interest because it has been considered as potential remedy for many kinds of disease. In this work, genistein in aqueous medium and in the presence of an host nanocarrier as amphiphilic cyclodextrin (CyD) modified in the upper rim with oligoethylene hydroxyl groups [(2-oligo(ethyleneoxide)-6-hexylthio)-beta-CyD, SC6OH] at 1:1 molar ratio, has been firstly investigated by UV-vis measurements coupled with circular dichroism data, in order to characterize the drug/macrocycle binding affinity through the formation of the complex. Furthermore, FTIR-ATR technique has been used to detect the complex formation in solid phase and to characterize the functional groups responsible of the solid Gen/SC6OH complex stability. The infrared absorbance spectra of the complex, collected in a wide range of wavenumber and around the physiological temperature, have been analysed and compared with the spectra of the pure compounds and their physical mixture. By monitoring the most significant changes in the shape and position of the absorbance bands of the Gen functional groups, we showed that the formation and/or modification of polar bonds play the main role in the interaction of the drug with the amphiphilic CyD. From the results, Gen is shown to be entangled in SC6OH nanoaggregates, establishing hydrogen bonding with the hydrophilic PEG chains.

UV–vis and FTIR-ATR characterization of 9-fluorenon-2-carboxyester/(2-hydroxypropyl)-β-cyclodextrin inclusion complex

In this work, the usefulness of (2-hydroxypropyl)-beta-cyclodextrin (HP-beta-CyD) as a tool to form an inclusion complex with 9-fluorenonic derivative (AG11) has been investigated, in pure water, by UV absorption. Phase-solubility diagrams allowed the determination of the association constant between AG11 and HP-beta-CyD. At the same time, solid binary systems between AG11 and HP-beta-CyD have been prepared in 1:1 stoichiometry by co-precipitation method. In order to confirm the complexation, FTIR spectroscopy in ATR geometry measurements have been performed and the results have been compared with the free compounds and the corresponding physical mixture in the same molar ratio. The nature of the interactions between AG11 and HP-beta-CyD has been elucidated also by applying mathematical procedures such as deconvolution and curve fitting. Improvement of the aqueous solubility is expected to improve the bioavailability of the drug in oral administration.

Amphiphilic Cyclodextrins as Nanocarriers of Genistein: A Spectroscopic Investigation Pointing Out the Structural Properties of the Host/Drug Complex System

Nanoggregates of nonionic amphiphilic cyclodextrin (ACyD) modified with hydrophobic chains of intermediate length [(2-oligo-ethyleneoxide-6-hexylthio)-beta-CyD, SC6OH] were prepared by emulsification-diffusion method. They are able to entrap an isoflavone, genistein (Gen), and the complexed species are studied at different host/guest molar ratio. The increased isoflavone solubility in the presence of the aggregates of SC6OH is investigated by UV-Vis spectroscopy, whereas size, charge, and structure of aggregates and their complexes with Gen are measured by means of static and quasi-elastic light scattering, and electrophoretic mobility measurements. On the other hand, preparing samples by the conventional method used for liposomes (hydration of an organic film of SC6OH and sonication) gives rise to aggregates with different sizes and lower colloidal stability. It is shown that the improved stability in water of ACyD aggregates both in the absence and in the presence of Gen, obtained by emulsification-diffusion is due to the existence of nanodomains of organic solvent (R(H) congruent with 120 nm) which cannot be completely removed by evaporation and freeze-drying and in which host/guest complexes are contained. This result shows that residues of organic solvent from preparation step favor the colloidal stability of the aggregate, but their presence must be taken into account in designing systems for drug delivery.

Structural and spectroscopic features of lutein/butanoyl-β-cyclodextrin nanoassemblies.

Lutein, the primary carotenoid present in the central area of the retina of eye appears to be associated with the protection against age-related macular degeneration (the leading cause of blindness in older adults). Its lipophilicity and consequently its scarce water solubility (1.3×10(-9)M) represent a drawback for bioavailability. To circumvent these unfavorable characteristics, in this work lutein (Lut) have been encapsulated in amphiphilic cyclodextrin (ACyD) by following the well-established strategy of entrapping a lipophilic drug in CyD carriers. Primary face butyrate modified β-cyclodextrins (C(4:7)) form in water nanoaggregates with a average size of 250nm and a ζ-potential of about -6mV. They are able to entrap lutein at 1:6 Lut/ACyD molar ratio by yielding nanoassemblies of vesicular aspect (320nm and -8mV) such as observed by static, dynamic and electrophoretic light-scattering. UV-vis measurements revealed that electronic properties of lutein were maintained when interact with ACyD nanoaggregates. The monitoring of the entapped carotenoid leaking from ACyD nanostructures was investigated suggesting the potential of Lut/ACyD nanoassemblies in drug delivery.