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Introduction: In light of the recent development of new soft materials, nanostructured self-assembled systems have attracted attention in a variety of technological fields of high social impact. Cyclodextrin nanosponges (CDNS) represent a new and highly versatile class of cross-linked cyclodextrin (CD)-based nanoporous polymers. Their intriguing properties, including safety, biodegradability, negligible toxicity, marked swelling behavior, superior inclusion capability with respect to native CD, are the bases for potential for applications in drug delivery, tissue engineering and regenerative medicine. Areas covered: We report on the state-of-art concerning a detailed characterization of structural and dynamical features of CDNS explored by the combined use of different and complementary techniques, such as Fourier transform infrared absorption in attenuated total reflectance geometry (FTIR-ATR) and Raman spectroscopies, and high resolution magic angle spinning (HR-MAS) NMR spectroscopy. The ambitious objective is to furnish an exhaustive survey of the role played by hydrophobic and hydrophilic groups within the cross-linked network, in dry and swollen states, in determining the macroscopic functional features of CDNS. Expert opinion: The reported results may significantly contribute in the rational design and optimization of new stimuli-responsive systems exhibiting tunable inclusion/release properties, adapted to the therapeutic demands of pathology.

The molecular mechanism responsible for the thermosensitive behaviour exhibited by pH-responsive cyclodextrin-based hydrogels is explored here with the twofold aim of clarifying some basic aspects of H-bond interactions in hydrogel phases and contributing to a future engineering of cyclodextrin hydrogels for targeted delivery and release of bioactive agents. The degree of H-bond association of water molecules entrapped in the gel network and the extent of intermolecular interactions involving the hydrophobic/hydrophilic moieties of the polymer matrix are probed by UV Raman and IR experiments, in order to address the question of how these different and complementary aspects combine to determine the pH-dependent thermal activation exhibited by these hydrogels. Complementary vibrational spectroscopies are conveniently employed in this study with the aim of safely disentangling the spectral response arising from the two main components of the hydrogel systems, i.e. the polymer matrix and water solvent. The experimental evidence suggests that the dominant effects in the mechanism of solvation of cyclodextrin-based hydrogels are due to the changes occurring, upon increasing of temperature, in the hydrophobicity character of specific chemical moieties of the polymer, as triggered by pH variations. The achievements of this work corroborate the potentiality of the UV Raman scattering technique, in combination with more conventional IR experiments, to provide a "molecular view" of complex macroscopic phenomena exhibited in hydrogel phases.

The effect of the inclusion into cyclodextrins (CD) cavity on the low-frequency vibrational dynamics of the anti-inflammatory drug ibuprofen (IBP) is here investigated by using Raman and inelastic neutron scattering (INS) experiments. The differences observed in the frequency regime 0-100 cm(-1) between the vibrational modes of uncomplexed racemic and enantiomeric IBP are discussed on the basis of comparison with the quantum chemical computation results, taking into account the distinct symmetry properties of the molecules involved in the formation of the host-guest complex. Subsequently, the inspection of the same frequency range in the spectra of pure host methyl-β-CD and its IBP-inclusion complexes allows one to identify significant modifications in the vibrational dynamics of the guest molecule after their confinement into CD cavity. The experimental Raman and neutron spectra and the derived Raman coupling function C(R)(ω) show that the complexation process gives rise to a complete amorphization of the drug, as well as to a partial hindering, in the vibrational dynamics of complexes, of the modes between 50 and 150 cm(-1) attributed to CD molecule. The comparison between the Raman and neutron spectra of free and complexed IBP in the energy range of the Boson peak (BP) gives evidence that the dynamics related to this specific vibrational feature is sensitive to complexation phenomena.

The vibrational dynamics of solid inclusion complexes of the nonsteroidal anti-inflammatory drug Ibuprofen (IBP) with beta-cyclodextrin (beta-CD) and methyl-beta-cyclodextrin (Me-beta-CD) has been investigated by using attenuated total reflection-Fourier transform infrared FTIR-ATR spectroscopy, in order to monitor the changes induced, as a consequence of complexation, on the vibrational spectrum of IBP, in the wavenumber range 600-4000 cm(-1). Quantum chemical calculations were performed on monomeric and dimeric structures of IBP, derived from symmetric hydrogen bonding of the two carboxylic groups, in order to unambiguously assign some characteristic IR bands in the IBP spectrum. The evolution in temperature from 250 to 340 K of the C horizontal lineO stretching vibration, described by a best-fit procedure, allowed us to extract the thermodynamic parameter DeltaH associated to the binding of IBP with betaCDs in the solid phase. By comparing these results, Me-beta-CD has been shown to be the most effective carrier for IBP.

Idebenone (IDE) is a powerful antioxidant that is potentially active towards cerebral diseases, but its low water solubility and fast first pass metabolism reduce its accumulation in the brain, making it ineffective. In this work, we developed cyclodextrin-based chitosan nanospheres (CS NPs) as potential carriers for nose-to-brain targeting of IDE. Sulfobutylether-β-cyclodextrin (SBE-β-CD) was used as a polyanion for chitosan (CS) and as a complexing agent for IDE, permitting its encapsulation into nanospheres (NPs) produced in an aqueous solution. Overloading NPs were obtained by adding the soluble IDE/hydroxypropyl-β-CD (IDE/HP-β-CD) inclusion complex into the CS or SBE-β-CD solutions. We obtained homogeneous CS NPs with a hydrodynamic radius of about 140 nm, positive zeta potential (about +28 mV), and good encapsulation efficiency and drug loading, particularly for overloaded NPs. A biphasic release of IDE, finished within 48 h, was observed from overloaded NPs, whilst non-overloaded CS NPs produced a prolonged release, without a burst effect. In vitro biological studies showed the ability of CS NPs to preserve the antioxidant activity of IDE on U373 culture cells. Furthermore, Fourier transform infrared spectroscopy (FT-IR) demonstrated the ability of CS NPs to interact with the excised bovine nasal mucosa, improving the permeation of the drug and potentially favoring its accumulation in the brain. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • EINS is applied to study molecular mobility of Gen/β-CDs inclusion complexes. • At ∼100 K a first anharmonic contribution, due to CH 3 rotations, is observed. • At higher T a second anharmonic process occurs, due to H-bond network relaxation. • The hindered mobility of inclusion complexes is due to "host-guest" interactions. • Dynamics was connected to stability, indicating HP-β-CD as the best carrier. Abstract Elastic incoherent neutron scattering was employed to investigate the molecular mobility of inclusion complexes, formed by two β-cyclodextrin (β-CD) derivatives, namely (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) and methyl-β-cyclodextrin (Me-β-CD), with Genistein (Gen), a phytoestrogen having antioxidant and anticarcinogenic activities, compared to the physical mixtures and single components. The results, collected in the 20–300 K temperature range, revealed a purely vibrational dynamics up to ∼100 K, where a first anharmonic contribution, corresponding to the methyl rotational dynamics, was observed and represented by an Arrhenius trend. At higher temperatures, a second anharmonic process, also found to obey an Arrhenius-like behavior, occurred at T d and was mainly ascribed to the relaxation of the H-bond network formed by host and guest molecules. Enthalpy and entropy changes associated to the activated anharmonic processes were obtained. The picoseconds timescale dynamics was finally connected to the thermal stability, suggesting HP-β-CD as the most effective carrier for Gen. [ABSTRACT FROM AUTHOR]

A vibrational study by means of UV-Raman and FTIR-ATR measurements has been performed on sulfobutyl ether β-cyclodextrin (SBE-β-CD)-water solutions, as a function of concentration and temperature, with the aim to provide a molecular-scale explanation of the enhanced performances as carrier agent exhibited by this modified macrocycle with respect to natural cyclodextrin. The attention has been mainly paid to the modifications induced on the vibrational band assigned to the O-H stretching intramolecular mode, in turn related to the dynamical rearrangement occurring in the hydrogen bonding (HB) network of water molecules. The results of our measurements clearly showed a characteristic "structure-breakerβ effect on the tetrahedral HB arrangements induced on water molecules by increasing of both temperature and solute concentration, allowing us to also extract thermodynamic parameters. These results could be a key step for a clearer understanding of the connection between the dynamical properties of hydration water and the complexing ability of this cyclodextrin derivative. [ABSTRACT FROM AUTHOR]

Highlights: [•] Resveratrol–sulfobutyl ether-β-cyclodextrin inclusion complex was prepared by freeze-drying. [•] Solubility phase studies and Job's plot method evidenced the presence in solution of a 1:1 inclusion complex. [•] FTIR-ATR analysis evidenced, in solid phase, the functional groups involved in the host–guest interactions. [•] Sulfobutyl ether-β-cyclodextrin improves anticancer activity of resveratrol on a human breast cancer cell line (MCF-7). [Copyright &y& Elsevier]

The swelling behaviour of β-cyclodextrin nanosponges, a new class of polymers obtained by reacting β-cyclodextrin with pyromellitic dianhydride, has been here investigated by the analysis of the vibrational dynamics performed by using Fourier-transform infrared spectroscopy in Attenuated Total Reflectance geometry and Raman scattering. The measurements have been carried out at different hydration levels and in the temperature range 250 K-310 K. The decomposition and assignment of the spectral components of the O-H stretching band have been discussed in terms of water molecules engaged in different hydrogen bonding networks, allowing us to recognize three different 'types' of water, namely 'bonded', 'intermediate'and 'free'. By following this approach, a detailed picture of the connectivity pattern of water molecules inside the polymeric matrix is achieved. The analysis of HOH bending vibrational band gives further information perfectly consistent with the results obtained from the analysis of the O-H stretching spectral region. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Hydroxypropyl-β-cyclodextrin (HP-β-CyD) and sulfobutyl ether-β-cyclodextrin (SBE-β-CyD) were used to generate hydrophilic complexes of the poorly water-soluble drug testosterone propionate (TP). The inclusion complexes were obtained by freeze-drying, and then analyzed at both liquid and solid states. Phase solubility studies, performed according to the type-A L solubility diagrams of TP in presence of both CyDs, suggested the formation of water-soluble complexes at 1:1 molar ratio. These results were confirmed by continuous variation method (Job’s plot). Both CyDs increased water-solubility of TP 100-fold as compared to the native drug. The host-guest arrangement of CyD complexes in a water solution was further investigated by one- and two-dimensional NMR spectroscopy, highlighting the insertion of the tetracyclic ring of TP into the CyD cavity, and the interaction of the pending ester chain of drug with the primary hydroxyl groups of CyDs at the narrow end of the toroid structure. In solid phase, FTIR-ATR spectroscopy showed that the C O stretching mode of the TP vibrational spectrum changed if the complex between the drug and CyDs occurred. This change is temperature-dependent, and its evolution, accounted for by deconvolution procedures, provided the thermodynamic parameters explaining the mechanisms involved in the formation of inclusion complexes. [ABSTRACT FROM AUTHOR]

An integrated experimental-numerical approach, basedon vibrationalspectroscopy techniques and quantum chemical computation methods,has been here implemented and tested on a new class of cyclodextrin-basedcross-linked polymers, namely, cyclodextrins nanosponges. By the simultaneousquantitative analysis of FTIR-ATR and Raman spectra in the frequencydomains between 1650–1800 and 3000–3700 cm–1, we individuated reliable physical descriptors directly connectedto the cross-linking degree of the polymeric matrices. The comparisonbetween the experimental data and the results of the quantum chemicalsimulations provided structural information on the involvement ofthe cyclodextrin chemical groups during the polymerization process.This proposed experimental numerical approach appears to be of generalapplication for the investigation of amorphous polymeric matricesof interest for technological application, for which the use of otherexperimental techniques is seriously hampered by the low or absentlevel of crystallinity. [ABSTRACT FROM AUTHOR]

The vibrational dynamics of cyclodextrin nanosponges(CDNS), anew class of nanostructured soft materials synthesized via cross-linkingreaction of natural cyclic oligosaccharide β-cyclodextrin (β-CD)with suitable organic reagents, is investigated by means of the combineduse of Raman and infrared spectroscopy, supported by numerical simulations.The vibrational spectra of the polymers show significant changes inthe frequency ranges 3000–3700 and 1500–1800 cm–1correlated to the relative amount of cross-linkerwith respect to monomeric CD. By using band deconvolution and best-fitprocedure of the experimental data and quantum chemical computations,a correlation between such changes and the degree of cross-linkingof the polymeric network is proposed. This experimental–numericalapproach, here applied to a model class of nanoporous polymeric systems,appears to be of general application for the study of polymeric matrixesof interest for biolife applications. [ABSTRACT FROM AUTHOR]

Abstract: The (R, S)-2-acetyl-1-(4′-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline ((R, S)-1) was previously identified as a potent non-competitive AMPA receptor antagonist able to prevent epileptic seizures and reduce AMPA-induced current in electrophysiological experiments. Through the enantiomeric resolution of racemate by chiral HPLC we already demonstrated that the (R)-1 enantiomer was the eutomer. Considering the poor water solubility, these compounds have been complexed with β-cyclodextrin (β-CyD). The effect of β-cyclodextrin on the spectral features of molecules was quantitatively investigated, in fully aqueous medium by phase-solubility study and the obtained diagrams suggested that it forms complexes with a molar ratio 1:1. The binding constant (K ( R )- 1 =15889M−1, K ( R , S )- 1 =1079 M−1) and the complexation efficiency (CE) were calculated. Then the solid complexes in 1:1 molar ratio were prepared by the co-precipitation method and the FTIR-ATR measurements were carried out in order to confirm the host–guest interactions that drive the complexation process, by monitoring the significant differences of the spectra of the complexes with respect to those of the corresponding physical mixtures in the same molar ratio. The experimental data have been compared with molecular modelling studies and we confirmed our hypothesis. [Copyright &y& Elsevier]