The effect of functionalizing lipid nanocapsules with NFL-TBS.40-63 peptide on their uptake by glioblastoma cells.

We previously described a neurofilament derived cell-penetrating peptide, NFL-TBS.40-63, that specifically enters in glioblastoma cells where it disturbs the microtubule network both in vitro and in vivo. The aim of this study is to test whether this peptide can increase the targeted uptake by glioblastoma cells of lipid nanocapsules filled with Paclitaxel, and thus can increase their anti-proliferation in vitro and in vivo. Here, using the drop tensiometry we show that approximately 60 NFL-TBS.40-63 peptides can bind to one 50 nm lipid nanocapsule. When nanocapsules are filled with a far-red fluorochrome (DiD) and Paclitaxel, the presence of the NFL-TBS.40-63 peptide increases their uptake by glioblastoma cells in culture as evaluated by FACS analysis, and thus reduces their proliferation. Finally, when such nanocapsules were injected in mice bearing a glioma tumour, they are preferentially targeted to the tumour and reduce its progression. These results show that nanocapsules functionalized with the NFL-TBS.40-63 peptide represent a powerful drug-carrier system for glioma targeted treatment

Spectral Bandwidth and WEC Performance Assessment

This paper investigates the dependency of wave energy conversion on the spectral bandwidth of sea-states. To this aim, the performance of an axisymmetrical Wave Energy Converter is assessed in the frequency domain by using a stochastic model in two far different wave climates (Portugal and North Sea) both represented by more than 23000 energy spectral densities obtained from measurements. The correlation between the performance and various bandwidth parameters found in the literature is observed. Then, refined methods for predicting the long-term converted wave energy based on wave statistics including spectral bandwidth are compared to more common procedures and conclusions are drawn

Disruption of Candida albicans IFF4 gene involves modifications of the cell electrical surface properties.

During the past two decades, the prevalence of candidiasis has increased markedly and Candida albicans has now become one of the most important causes of nosocomial infections, especially after colonization of inert surfaces such as catheters or prostheses. In a previous report, we demonstrated the overexpression of 35 unidentified genes in response to adherence of C. albicans germ tubes to plastic. Therefore, a bioinformatic analysis was performed searching for genes encoding surface proteins potentially involved in adherence. Nineteen genes were thus selected, and one of them, CaIFF4, was further investigated. The deduced protein of this CaIFF4 gene revealed a glycosylphosphatidylinositol (GPI)-anchored site as well as the presence of a N-terminal signal peptide. Disruption of both alleles of CaIFF4 gene from C. albicans parent strain BWP17 was performed by PCR method. Then investigations of properties of null mutant for CaIFF4 gene showed a decrease of adherence of germ tubes to plastic in comparison to the parent strain BWP17. Besides, electrophoretic mobilities of germ tubes of CaIFF4 null mutant and of parental strain BWP17 were measured. Data were then analysed with soft particles analysis theory. Results point out a less important electrophoretic mobility of germ tubes of CaIFF4 null mutant in comparison to germ tubes of BWP17 parental strain

Stress Conditions Induced by Carvacrol and Cinnamaldehyde on Acinetobacter baumannii

Acinetobacter baumannii has emerged as a major cause of nosocomial infections. The ability of A. baumannii to display various resistance mechanisms against antibiotics has transformed it into a successful nosocomial pathogen. The limited number of antibiotics in development and the disengagement of the pharmaceutical industry have prompted the development of innovative strategies. One of these strategies is the use of essential oils, especially aromatic compounds that are potent antibacterial molecules. Among them, the combination of carvacrol and cinnamaldehyde has already demonstrated antibacterial efficacy against A. baumannii. The aim of this study was to determine the biological effects of these two compounds in A. baumannii, describing their effect on the rRNA and gene regulation under environmental stress conditions. Results demonstrated rRNA degradation by the carvacrol/cinnamaldehyde mixture, and this effect was due to carvacrol. Degradation was conserved after encapsulation of the mixture in lipid nanocapsules. Results showed an upregulation of the genes coding for heat shock proteins, such as groES, groEL, dnaK, clpB, and the catalase katE, after exposure to carvacrol/cinnamaldehyde mixture. The catalase was upregulated after carvacrol exposure wich is related to an oxidative stress. The combination of thiourea (hydroxyl radical scavenger) and carvacrol demonstrated a potent bactericidal effect. These results underline the development of defense strategies of the bacteria by synthesis of reactive oxygen species in response to environmental stress conditions, such as carvacrol

Distribution of lipid nanocapsules in different cochlear cell populations after round window membrane permeation

Hearing loss is a major public health problem, and its treatment with traditional therapy strategies is often unsuccessful due to limited drug access deep in the temporal bone. Multifunctional nanoparticles that are targeted to specified cell populations, biodegradable, traceable in vivo, and equipped with controlled drug/gene release may resolve this problem. We developed lipid core nanocapsules (LNCs) with sizes below 50 nm. The aim of the present study is to evaluate the ability of the LNCs to pass through the round window membrane and reach inner ear targets. FITC was incorporated as a tag for the LNCs and Nile Red was encapsulated inside the oily core to assess the integrity of the LNCs. The capability of LNCs to pass through the round window membrane and the distribution of the LNCs inside the inner ear were evaluated in rats via confocal microscopy in combination with image analysis using ImageJ. After round window membrane administration, LNCs reached the spiral ganglion cells, nerve fibers, and spiral ligament fibrocytes within 30 min. The paracellular pathway was the main approach for LNC penetration of the round window membrane. LNCs can also reach the vestibule, middle ear mucosa, and the adjacent artery. Nuclear localization was detected in the spiral ganglion, though infrequently. These results suggest that LNCs are potential vectors for drug delivery into the spiral ganglion cells, nerve fibers, hair cells, and spiral ligament

In vitro and in vivo behaviour of paclitaxel loaded lipid nanocapsules

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Internalisation par les oligodendrocytes de nanocapsules lipidiques vectorisées

Introduction Les nanoparticules lipidiques (LNC) constituent un vecteur potentiel de thérapeutiques ciblées à l’échelon cellulaire. Nous avons étudié leur intérêt pour atteindre spécifiquement les oligodendocytes (OL). Objectifs Étudier la pénétration éventuelle de LNC vectorisées avec un peptide (NFL-TBS) que nous avions identifié comme pénétrant dans les OL par endocytose et aux effets proremyélinisants (Fressinaud et Eyer, 2015). Patients et méthodes Les cultures d’OL de rats, en milieu chimiquement défini, étaient traitées par différentes concentrations de LNC identifiées par un fluorochrome (DiD) et adsorbées ou non avec le peptide NFL-TBS. Leur effet sur le développement des OL était observé. La colocalisation intracellulaire du DiD et des marqueurs immunocytochimiques des OL (A2B5, CNP, MBP) était détectée par microscopie confocale (triple/quadruple marquage) et les OL ayant incorporé les LNC étaient quantifiés. Trois expériences étaient tripliquées. Résultats L’adsorption de NFL-TBS permettait la pénétration des LNC dans la majorité des OL, la colocalisation du DiD et des différents marqueurs d’OL confirmant la situation intracellulaire des LNC. La présence des LNC DiD + était abondante et aisément identifiable après quelques heures dans le corps cellulaire. Aucun effet négatif de la présence des LNC n’était observé après plusieurs jours à concentration optimale. Discussion L’internalisation de LNC de taille et concentration optimales n’altère pas le développement des OL. Ces particules représentent de potentiels vecteurs de molécules à visée thérapeutique dans la SEP. Conclusion L’internalisation par les OL in vitro des nanocapsules lipidiques fonctionnalisées par le peptide NFL-TBS, suggère leur éventuel potentiel pour servir de vecteur délivrant des molécules thérapeutiques au cours de la SEP

Dewetting of thin polymer films near the glass transition

Dewetting of ultra-thin polymer films near the glass transition exhibits unexpected front morphologies [G. Reiter, Phys. Rev. Lett., 87, 186101 (2001)]. We present here the first theoretical attempt to understand these features, focusing on the shear-thinning behaviour of these films. We analyse the profile of the dewetting film, and characterize the time evolution of the dry region radius, $R_{d}(t)$, and of the rim height, $h_{m}(t)$. After a transient time depending on the initial thickness, $h_{m}(t)$ grows like $\sqrt{t}$ while $R_{d}(t)$ increases like $\exp{(\sqrt{t})}$. Different regimes of growth are expected, depending on the initial film thickness and experimental time range.Comment: 4 pages, 5 figures Revised version, published in Physical Review Letters: F. Saulnier, E. Raphael and P.-G. de Gennes, Phys. Rev. Lett. 88, 196101 (2002