Clonidine complexation with hydroxypropyl-beta-cyclodextrin: From physico-chemical characterization to in vivo adjuvant effect in local anesthesia.

Clonidine (CND), an alpha-2-adrenergic agonist, is used as an adjuvant with local anesthetics. In this work, we describe the preparation and characterization of an inclusion complex of clonidine in hydroxypropyl-beta-cyclodextrin (HP-ß-CD), as revealed by experimental (UV-vis absorption, SEM, X-ray diffraction, DOSY- and ROESY-NMR) and theoretical (molecular dynamics) approaches. CND was found to bind to HP-ß-CD (Ka=20M(-1)) in 1:1 stoichiometry. X-ray diffractograms and SEM images provided evidence of inclusion complex formation, which was associated with changes in the diffraction patterns of the pure compounds. NMR experiments revealed changes in the chemical shift of H3HP-ß-CD hydrogens (Δ=0.026ppm) that were compatible with the insertion of CND in the hydrophobic cavity of the cyclodextrin. Molecular dynamics simulation with the three CND species that exist at pH 7.4 revealed the formation of intermolecular hydrogen bonds, especially for the neutral imino form of CND, which favored its insertion in the HP-ß-CD cavity. In vitro assays revealed that complexation retarded drug diffusion without changing the intrinsic toxicity of clonidine, while in vivo tests in rats showed enhanced sensory blockade after the administration of 0.15% CND, with the effect decreasing in the order: CND:HP-ß-CD+bupivacaine>CND+bupivacaine>bupivacaine>CND:HP-ß-CD>clonidine. The findings demonstrated the suitability of the complex for use as a drug delivery system for clinical use in antinociceptive procedures, in association with local anesthetics.

Charge carriers and small-polaron migration as the origin of intrinsic dielectric anomalies in multiferroic TbMnO3 polycrystals.

Temperature-dependent and frequency-dependent dielectric investigations have been performed in TbMnO3 polycrystals sintered in either oxidative or reductive atmospheres. The results revealed the occurrence of two dielectric anomalies above 100 K, which are caused by the thermal activation of charge carriers and their motion in grain cores and grain boundaries. The temperature dependence of the bulk dc conductivity was also analysed and indicates that charge carriers move between inequivalent sites according to a variable-range-hopping mechanism. Also, a strong correlation between dielectric properties and crystalline structure was observed. Furthermore, a low-temperature dielectric relaxation, commonly reported in rare-earth manganite crystals, was observed in both samples. This relaxation follows the empirical Cole-Cole model and was attributed to small-polaron tunnelling. Polaron motion was observed to be affected by the magnetic transitions, structural properties and intrinsic anisotropies in TbMnO3. It is also worth mentioning that the dielectric anomaly due to motion of charge carriers in grain boundaries is the only one of extrinsic origin, while the anomalies related to carrier motion in grain cores and small-polaron tunnelling are intrinsic to TbMnO3.

Cycloidal order of 4f moments as a probe of chiral domains in DyMnO3.

Using soft x-ray diffraction at the Dy-M5 resonance, pronounced circular dichroism in the ferroelectric phase of DyMnO3 is observed in connection with sizable b and c components of the Dy-4f magnetic moments. This provides strong evidence for cycloidal order of the 4f moments, corroborating that inversion-symmetry breaking in this material is not accomplished by the Mn spins alone. The 4f circular dichroism allows us to image multiferroic domains that are imprinted on the surface of DyMnO3 using the local charging by the x-ray beam via the photoelectric effect.

Inclusion complex of S(-) bupivacaine and 2-hydroxypropyl-beta-cyclodextrin: study of morphology and cytotoxicity

Local anesthetics (LA) belong to a class of pharmacological compounds that attenuate or eliminate pain by binding to the sodium channel of excitable membranes, blocking the influx of sodium ions and the propagation of the nerve impulse. S (-) bupivacaine (S(-)bvc) is a local anesthetic of amino-amide type, widely used in surgery and obstetrics for sustained peripheraland central nerve blockade. This article focuses on the characterization of an inclusion complex of S(-) bvc in2-hydroxypropyl- beta-cyclodextrin (HP-beta -CD). Differential scanning calorimetry, scanning electron microscopy andX-Ray diffraction analysis showed structural changes inthe complex. In preliminary toxicity studies, the cellviability tests revealed that the inclusion complex decreased the toxic effect (p smaller that 0.001) produced by S(-) bvc.These results suggest that the S(-) bvc:HP- beta-CD inclusion complex represents a promising agent for the treatment of regional pain.

High-resolution X-ray diffraction beamline at the LNLS for the study of charge, orbital and magnetic structures.

A high-resolution X-ray diffraction beamline at the Brazilian Synchrotron Light Laboratory (LNLS) has been commissioned for the study of crystalline magnetic materials. The beamline optics is based on a Rh-coated vertical-focusing X-ray mirror and a sagittal-focusing double-crystal monochromator. The primary instrument is a six-circle diffractometer equipped with energy and polarization analysers and a closed-cycle He cryostat. The beamline source is a bending magnet of the 1.37 GeV storage ring of the LNLS, delivering approximately 4 x 10(10) photons s(-1) at 8 keV at the sample position. Resonant and non-resonant scattering are the main techniques used to study charge, orbital and magnetic structures. Examples of magnetic scattering in Ho and NiO single crystals, as well as orbital ordering in manganites thin films, are presented.