In Vitro Evaluation of Curcumin- and Quercetin-Loaded Nanoemulsions for Intranasal Administration: Effect of Surface Charge and Viscosity

The nose-to-brain delivery of neuroprotective natural compounds is an appealing approach for the treatment of neurodegenerative diseases. Nanoemulsions containing curcumin (CUR) and quercetin (QU) were prepared by high-pressure homogenization and characterized physicochemically and structurally. A negative (CQ_NE—), a positive (CQ_NE+), and a gel (CQ_NEgel) formulation were developed. The mean particle size of the CQ_NE— and CQ_NE+ was below 120 nm, while this increased to 240 nm for the CQ_NEgel. The formulations showed high encapsulation efficiency and protected the CUR/QU from biological/chemical degradation. Electron paramagnetic resonance spectroscopy showed that the CUR/QU were located at the interface of the oil phase in the proximity of the surfactant layer. The cytotoxicity studies showed that the formulations containing CUR/QU protected human nasal cells from the toxicity evidenced for blank NEs. No permeation across an in vitro model nasal epithelium was evidenced for CUR/QU, probably due to their poor water-solubility and instability in physiological buffers. However, the nasal cells' drug uptake showed that the total amount of CUR/QU in the cells was related to the NE characteristics (CQ NE— > CQ NE+ > CQ_NEgel). The method used allowed the obtainment of nanocarriers of an appropriate size for nasal administration. The treatment of the cells showed the protection of cellular viability, holding promise as an anti-inflammatory treatment able to prevent neurodegenerative diseases

Emergent chiroptical properties in supramolecular and plasmonic assemblies

This tutorial provides a comprehensive description of the origin of chiroptical properties of supramolecular and plasmonic assemblies in the UV-visible region of the electromagnetic spectrum. The photophysical concepts essential for understanding chiroptical signatures are presented in the first section. Just as the oscillator strength (a positive quantity) is related to absorption, the rotational strength (either a positive or a negative quantity) defines the emergence of chiroptical signatures in molecular/plasmonic systems. In supramolecular systems, induced circular dichroism (ICD) originates through the off-resonance coupling of transition dipoles in chiral inclusion complexes, while exciton coupled circular dichroism (ECD) originates through the on-resonance exciton coupling of transition dipoles in chiral assemblies resulting in the formation of a bisignated CD signal. In bisignated ECD spectra, the sign of the couplet is determined not only by the handedness of chiral supramolecular assemblies, but also by the sign of the interaction energy between transition dipoles. Plasmonic chirality is briefly addressed in the last section, focusing on inherent chirality, induced chirality, and surface plasmon-coupled circular dichroism (SP-CD). The oscillator strength is of the order of 1 in molecular systems, while it becomes very large (104-105) in plasmonic systems due to the collective plasmonic excitations, resulting in intense CD signals, which can be exploited for the design of plasmonic metamaterial platforms for chiral sensing applications. This journal i

Improvement of imiquimod solubilization and skin retention via tpgs micelles: Exploiting the co-solubilizing effect of oleic acid

Imiquimod (IMQ) is an immunostimulant drug approved for the topical treatment of actinic keratosis, external genital-perianal warts as well as superficial basal cell carcinoma that is used off-label for the treatment of different forms of skin cancers, including some malignant melanocytic proliferations such as lentigo maligna, atypical nevi and other in situ melanoma-related diseases. Imiquimod skin delivery has proven to be a real challenge due to its very low water-solubility and reduced skin penetration capacity. The aim of the work was to improve the drug solubility and skin retention using micelles of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), a water-soluble derivative of vitamin E, co-encapsulating various lipophilic compounds with the potential ability to improve imiquimod affinity for the micellar core, and thus its loading into the nanocarrier. The formulations were characterized in terms of particle size, zeta potential and stability over time and micelles performance on the skin was evaluated through the quantification of imiquimod retention in the skin layers and the visualization of a micelle-loaded fluorescent dye by two-photon microscopy. The results showed that imiquimod solubility strictly depends on the nature and concentration of the co-encapsulated compounds. The micellar formulation based on TPGS and oleic acid was identified as the most interesting in terms of both drug solubility (which was increased from few µg/mL to 1154.01 ± 112.78 µg/mL) and micellar stability (which was evaluated up to 6 months from micelles preparation). The delivery efficiency after the application of this formulation alone or incorporated in hydrogels showed to be 42-and 25-folds higher than the one of the commercial creams

Characterizing HR3549B using SPHERE

Aims. In this work, we characterize the low mass companion of the A0 field star HR3549. Methods. We observed HR3549AB in imaging mode with the the NIR branch (IFS and IRDIS) of SPHERE@VLT, with IFS in YJ mode and IRDIS in the H band. We also acquired a medium resolution spectrum with the IRDIS long slit spectroscopy mode. The data were reduced using the dedicated SPHERE GTO pipeline, purposely designed for this instrument. We employed algorithms such as PCA and TLOCI to reduce the speckle noise. Results. The companion was clearly visible both with IRDIS and IFS.We obtained photometry in four different bands as well as the astrometric position for the companion. Based on our astrometry, we confirm that it is a bound object and put constraints on its orbit. Although several uncertainties are still present, we estimate an age of ~100-150 Myr for this system, yielding a most probable mass for the companion of 40-50MJup and T_eff ~300-2400 K. Comparing with template spectra points to a spectral type between M9 and L0 for the companion, commensurate with its position on the color-magnitude diagram.Comment: Accepted by A&A, 13 pages, 10 Figures (Figures 9 and 10 degraded to reduce the dimension

Dye-Loaded Quatsomes Exhibiting FRET as Nanoprobes for Bioimaging

Fluorescent organic nanoparticles (FONs) are emerging as an attractive alternative to the well-established fluorescent inorganic nanoparticles or small organic dyes. Their proper design allows one to obtain biocompatible probes with superior brightness and high photostability, although usually affected by low colloidal stability. Herein, we present a type of FONs with outstanding photophysical and physicochemical properties in-line with the stringent requirements for biomedical applications. These FONs are based on quatsome (QS) nanovesicles containing a pair of fluorescent carbocyanine molecules that give rise to Förster resonance energy transfer (FRET). Structural homogeneity, high brightness, photostability, and high FRET efficiency make these FONs a promising class of optical bioprobes. Loaded QSs have been used for in vitro bioimaging, demonstrating the nanovesicle membrane integrity after cell internalization, and the possibility to monitor the intracellular vesicle fate. Taken together, the proposed QSs loaded with a FRET pair constitute a promising platform for bioimaging and theranostics

Circularly Polarized Luminescence from New Heteroleptic Eu(III) and Tb(III) Complexes

The complexes [Eu(bpcd)(tta)], [Eu(bpcd)(Coum)], and [Tb(bpcd)(Coum)] [tta = 2-thenoyltrifluoroacetyl-acetonate, Coum = 3-acetyl-4-hydroxy-coumarin, and bpcd = N,N′-bis(2-pyridylmethyl)-trans-1,2-diaminocyclohexane-N,N′-diacetate] have been synthesized and characterized from photophysical and thermodynamic points of view. The optical and chiroptical properties of these complexes, such as the total luminescence, decay curves of the Ln(III) luminescence, electronic circular dichroism, and circularly polarized luminescence, have been investigated. Interestingly, the number of coordinated solvent (methanol) molecules is sensitive to the nature of the metal ion. This number, estimated by spectroscopy, is >1 for Eu(III)-based complexes and <1 for Tb(III)-based complexes. A possible explanation for this behavior is provided via the study of the minimum energy structure obtained by density functional theory (DFT) calculations on the model complexes of the diamagnetic Y(III) and La(III) counterparts [Y(bpcd)(tta)], [Y(bpcd)(Coum)], and [La(bpcd)(Coum)]. By time-dependent DFT calculations, estimation of donor-acceptor (D-A) distances and of the energy position of the S1and T1ligand excited states involved in the antenna effect was possible. These data are useful for rationalizing the different sensitization efficiencies (ηsens) of the antennae toward Eu(III) and Tb(III). The tta ligand is an optimal antenna for sensitizing Eu(III) luminescence, while the Coum ligand sensitizes better Tb(III) luminescence {φovl= 55%; ηsens≥ 55% for the [Tb(bpcd)(Coum)] complex}. Finally, for the [Eu(bpcd)(tta)] complex, a sizable value of glum(0.26) and a good quantum yield (26%) were measured

A narrow, edge-on disk resolved around HD 106906 with SPHERE

HD~106906AB is so far the only young binary system around which a planet has been imaged and a debris disk evidenced thanks to a strong IR excess. As such, it represents a unique opportunity to study the dynamics of young planetary systems. We aim at further investigating the close (tens of au scales) environment of the HD~106906AB system. We used the extreme AO fed, high contrast imager SPHERE recently installed on the VLT to observe HD~106906. Both the IRDIS imager and the Integral Field Spectrometer were used. We discovered a very inclined, ring-like disk at a distance of 65~au from the star. The disk shows a strong brightness asymmetry with respect to its semi-major axis. It shows a smooth outer edge, compatible with ejection of small grains by the stellar radiation pressure. We show furthermore that the planet's projected position is significantly above the disk's PA. Given the determined disk inclination, it is not excluded though that the planet could still orbit within the disk plane if at a large separation (2000--3000 au). We identified several additional point sources in the SPHERE/IRDIS field-of-view, that appear to be background objects. We compare this system with other debris disks sharing similarities, and we briefly discuss the present results in the framework of dynamical evolution.Comment: 7 pages, 6 figures, accepted by Astronomy & Astrophysic

Shadows and spirals in the protoplanetary disk HD 100453

Understanding the diversity of planets requires to study the morphology and the physical conditions in the protoplanetary disks in which they form. We observed and spatially resolved the disk around the ~10 Myr old protoplanetary disk HD 100453 in polarized scattered light with SPHERE/VLT at optical and near-infrared wavelengths, reaching an angular resolution of ~0.02", and an inner working angle of ~0.09". We detect polarized scattered light up to ~0.42" (~48 au) and detect a cavity, a rim with azimuthal brightness variations at an inclination of 38 degrees, two shadows and two symmetric spiral arms. The spiral arms originate near the location of the shadows, close to the semi major axis. We detect a faint spiral-like feature in the SW that can be interpreted as the scattering surface of the bottom side of the disk, if the disk is tidally truncated by the M-dwarf companion currently seen at a projected distance of ~119 au. We construct a radiative transfer model that accounts for the main characteristics of the features with an inner and outer disk misaligned by ~72 degrees. The azimuthal brightness variations along the rim are well reproduced with the scattering phase function of the model. While spirals can be triggered by the tidal interaction with the companion, the close proximity of the spirals to the shadows suggests that the shadows could also play a role. The change in stellar illumination along the rim, induces an azimuthal variation of the scale height that can contribute to the brightness variations. Dark regions in polarized images of transition disks are now detected in a handful of disks and often interpreted as shadows due to a misaligned inner disk. The origin of such a misalignment in HD 100453, and of the spirals, is unclear, and might be due to a yet-undetected massive companion inside the cavity, and on an inclined orbit.Comment: A&A, accepte

Multi-band high resolution spectroscopy rules out the hot Jupiter BD+20 1790b - First data from the GIARPS Commissioning

Context. Stellar activity is currently challenging the detection of young planets via the radial velocity (RV) technique. Aims. We attempt to definitively discriminate the nature of the RV variations for the young active K5 star BD+20 1790, for which visible (VIS) RV measurements show divergent results on the existence of a substellar companion. Methods. We compare VIS data with high precision RVs in the near infrared (NIR) range by using the GIANO - B and IGRINS spectrographs. In addition, we present for the first time simultaneous VIS-NIR observations obtained with GIARPS (GIANO - B and HARPS - N) at Telescopio Nazionale Galileo (TNG). Orbital RVs are achromatic, so the RV amplitude does not change at different wavelengths, while stellar activity induces wavelength-dependent RV variations, which are significantly reduced in the NIR range with respect to the VIS. Results. The NIR radial velocity measurements from GIANO - B and IGRINS show an average amplitude of about one quarter with respect to previously published VIS data, as expected when the RV jitter is due to stellar activity. Coeval multi-band photometry surprisingly shows larger amplitudes in the NIR range, explainable with a mixture of cool and hot spots in the same active region. Conclusions. In this work, the claimed massive planet around BD+20 1790 is ruled out by our data. We exploited the crucial role of multi- wavelength spectroscopy when observing young active stars: thanks to facilities like GIARPS that provide simultaneous observations, this method can reach its maximum potential.Comment: 12 pages, 7 figure