Brain delivery of vasoactive intestinal peptide (VIP) following nasal administration to rats

The aim of this work was to study in rats the nasal route for the brain delivery of the vasoactive intestinal peptide (VIP) neuropeptide. After evaluating VIP stability in solutions obtained from nasal washes, the effect of formulation parameters (pH 4-9, 0-1% (w/v) lauroylcarnitine (LC), hypo- or isoosmolality) on the brain uptake of intranasally administered VIP (10(-8)M)/125I-VIP (300,000 cpm/ml) was studied, using an in situ perfusion technique. Brain radioactivity distribution was assessed by quantitative autoradiographic analysis. Results were compared to intravenously administered VIP. With a hypotonic formulation at pH 4 containing 0.1% LC and 1% bovine serum albumin, VIP stability was satisfactory and loss by adsorption was minimal. Using this formulation, around 0.11% of initial radioactivity was found in the brain after 30 min perfusion and was located in the olfactory bulbs, the midbrain and the cerebellum. HPLC analysis of brain and blood extracts demonstrated the presence of intact VIP in brain and its complete degradation in the blood compartment. By intravenous administration, no intact VIP was found either in brain or in blood. In conclusion, intact VIP could be delivered successfully to the brain using the intranasal route for administration

Offset fields in perpendicularly magnetized tunnel junctions

We study the offset fields affecting the free layer of perpendicularly magnetized tunnel junctions. In extended films, the free layer offset field results from interlayer exchange coupling with the reference layer through the MgO tunnel oxide. The free layer offset field is thus accompanied with a shift of the free layer and reference layer ferromagnetic resonance frequencies. The shifts depend on the mutual orientation of the two magnetizations. The offset field decreases with the resistance area product of the tunnel oxide. Patterning the tunnel junction into an STT-MRAM disk-shaped cell changes substantially the offset field, as the reduction of the lateral dimension comes with the generation of stray fields by the reference and the hard layer. The experimental offset field compares best with the spatial average of the sum of these stray fields, thereby providing guidelines for the offset field engineering.Comment: Special issue of J. Phys. D: Appl. Phys (2019) on STT-MRA

Anticancer drug delivery with transferrin targeted polymeric chitosan vesicles

The study reports the initial biological evaluation of targeted polymeric glycol chitosan vesicles as carrier systems for doxorubicin (Dox). Transferrin (Tf) was covalently bound to the Dox-loaded palmitoylated glycol chitosan (GCP) vesicles using dimethylsuberimidate (DMSI). For comparison, glucose targeted niosomes were prepared using N-palmitoyl glucosamine. Biological properties were studied using confocal microscopy, flow cytometry, and cytotoxicity assays as well as a mouse xenograft model. Tf vesicles were taken up rapidly with a plateau after 1-2 h and Dox reached the nucleus after 60-90 min. Uptake was not increased with the use of glucose ligands, but higher uptake and increased cytotoxicity were observed for Tf targeted as compared to GCP Dox alone. In the drug-resistant A2780AD cells and in A431 cells, the relative increase in activity was significantly higher for the Tf-GCP vesicles than would have been expected from the uptake studies. All vesicle formulations had a superior in vivo safety profile compared to the free drug. The in vitro advantage of targeted Tf vesicles did not translate into a therapeutic advantage in vivo. All vesicles reduced tumor size on day 2 but were overall less active than the free drug

Annealing stability of magnetic tunnel junctions based on dual MgO free layers and [Co/Ni] based thin synthetic antiferromagnet fixed system

We study the annealing stability of bottom-pinned perpendicularly magnetized magnetic tunnel junctions based on dual MgO free layers and thin fixed systems comprising a hard [Co/Ni] multilayer antiferromagnetically coupled to thin a Co reference layer and a FeCoB polarizing layer. Using conventional magnetometry and advanced broadband ferromagnetic resonance, we identify the properties of each sub-unit of the magnetic tunnel junction and demonstrate that this material option can ensure a satisfactory resilience to the 400$^\circ$C thermal annealing needed in solid-state magnetic memory applications. The dual MgO free layer possesses an anneal-robust 0.4 T effective anisotropy and suffers only a minor increase of its Gilbert damping from 0.007 to 0.010 for the toughest annealing conditions. Within the fixed system, the ferro-coupler and texture-breaking TaFeCoB layer keeps an interlayer exchange above 0.8 mJ/m$^2$, while the Ru antiferrocoupler layer within the synthetic antiferromagnet maintains a coupling above -0.5 mJ/m$^2$. These two strong couplings maintain the overall functionality of the tunnel junction upon the toughest annealing despite the gradual degradation of the thin Co layer anisotropy that may reduce the operation margin in spin torque memory applications. Based on these findings, we propose further optimization routes for the next generation magnetic tunnel junctions

Niosomes and polymeric chitosan based vesicles bearing transferrin and glucose ligands for drug targeting

PURPOSE: To prepare polymeric vesicles and niosomes bearing glucose or transferrin ligands for drug targeting. METHODS: A glucose-palmitoyl glycol chitosan (PGC) conjugate was synthesised and glucose-PGC polymeric vesicles prepared by sonication of glucose-PGC/cholesterol. N-palmitoylglucosamine (NPG) was synthesised and NPG niosomes also prepared by sonication of NPG/ sorbitan monostearate/ cholesterol/ cholesteryl poly-24-oxyethylene ether. These 2 glucose vesicles were incubated with colloidal concanavalin A gold (Con-A gold), washed and visualised by transmission electron microscopy (TEM). Transferrin was also conjugated to the surface of PGC vesicles and the uptake of these vesicles investigated in the A431 cell line (over expressing the transferrin receptor) by fluorescent activated cell sorter analysis. RESULTS: TEM imaging confirmed the presence of glucose units on the surface of PGC polymeric vesicles and NPG niosomes. Transferrin was coupled to PGC vesicles at a level of 0.60+/-0.18 g of transferrin per g polymer. The proportion of FITC-dextran positive A431 cells was 42% (FITC-dextran solution), 74% (plain vesicles) and 90% (transferrin vesicles). CONCLUSIONS: Glucose and transferrin bearing chitosan based vesicles and glucose niosomes have been prepared. Glucose bearing vesicles bind Con-A to their surface. Chitosan based vesicles are taken up by A431 cells and transferrin enhances this uptake

Diet, cancer, and the lipidome.

International audienceThe potential for dietary fat to interfere with the development of breast cancer by delaying its occurrence makes the identification of defined molecules a mandatory step in cancer prevention. In order to circumvent the limitations and/or bias of dietary exposure assessment tools, biomarkers of past lipid intake such as the fatty acid composition of white adipose tissue have been used. When considered separately, candidate fatty acids identified as favorable on the basis of their association with breast cancer risk have usually led to inconsistent results in animal intervention studies. This inconsistency indicates that any approach based on a single fatty acid should be abandoned for an integrated view over the complex lipid interactions which finally determines the lipidome, the lipid profile that is found in individuals. This article presents a reappraisal of the role of the lipid profile through a comprehensive reanalysis of adipose tissue fatty acid composition obtained in patients with benign or malignant breast tumors as well as in experimental animals during dietary interventions. Rather than a single fatty acid, a composite indicator combining elevated monounsaturates and low omega6/omega3 fatty acid ratio was associated with breast cancer protection. This lipidome may become the template for identifying breast cancer risk related to diet, and for designing proper dietary modifications to delay the occurrence of breast cancer, although the universality of the findings cannot be assessed from a single study

Time-resolved spin-torque switching in MgO-based perpendicularly magnetized tunnel junctions

We study ns scale spin-torque-induced switching in perpendicularly magnetized tunnel junctions (pMTJ). Although the switching voltages match with the macrospin instability threshold, the electrical signatures of the reversal indicate the presence of domain walls in junctions of various sizes. In the antiparallel (AP) to parallel (P) switching, a nucleation phase is followed by an irreversible flow of a wall through the sample at an average velocity of 40 m/s with back and forth oscillation movements indicating a Walker propagation regime. A model with a single-wall locally responding to the spin-torque reproduces the essential dynamical signatures of the reversal. The P to AP transition has a complex dynamics with dynamical back-hopping whose probability increases with voltage. We attribute this back-hopping to the instability of the nominally fixed layers