Self-assembled biotransesterified cyclodextrins as potential Artemisinin nanocarriers. II: In vitro behavior toward the immune system and in vivo biodistribution assessment of unloaded nanoparticles.

In a previous study, we reported on the formulation of Artemisinin-loaded surface-decorated nanoparticles (nanospheres and nanoreservoirs) by co-nanoprecipitation of PEG derivatives (PEG1500 and PEG4000-stearate, polysorbate 80) and biosynthesized γ-CD fatty esters. In the present study, the co-nanoprecipitation was extended to the use of a PEGylated phospholipid, namely DMPE-PEG2000. As our goal was to prepare long-circulating nanocarriers for further systemic delivery of Artemisinin (ART), here, we have investigated, on the one hand, the in vitro behavior of these surface-modified γ-CD-C10 particles toward the immune system (complement activation and macrophage uptake assays) and, on the other hand, their biodistribution features in mice. These experiments showed that the in vitro plasma protein adsorption and phagocytosis by macrophage cells triggered by γ-CD-C10 nanoparticles were significantly reduced when their surface was decorated with amphiphilic PEGylated molecules, in particular PEG1500-stearate, DMPE-mPEG2000 or polysorbate 80. The prolonged blood circulation time assessed by fluorescence imaging was demonstrated for unloaded γ-CD-C10-based nanospheres and nanoreservoir particles containing DMPE-PEG2000 and polysorbate80, respectively. These nanoparticles also proved to be non-hemolytic at the concentration range used in vivo. Within the limits of the conducted experiments, the co-nanoprecipitation technique may be considered as an alternative for surface modification of amphiphilic CD-based drug delivery systems and may be applied to the systemic delivery of ART

Characterization of function of the GlgA2 glycogen/starch synthase in Cyanobacterium sp. Clg1 highlights convergent evolution of glycogen metabolism into starch granule aggregation

At variance with the starch-accumulating plants and most of the glycogen-accumulating cyanobacteria, Cyanobacterium sp. CLg1 synthesizes both glycogen and starch. We now report the selection of a starchless mutant of this cyanobacterium that retains wild-type amounts of glycogen. Unlike other mutants of this type found in plants and cyanobacteria, this mutant proved to be selectively defective for one of the two types of glycogen/starch synthase: GlgA2. This enzyme is phylogenetically related to the previously reported SSIII/SSIV starch synthase that is thought to be involved in starch granule seeding in plants. This suggests that, in addition to the selective polysaccharide debranching demonstrated to be responsible for starch rather than glycogen synthesis, the nature and properties of the elongation enzyme define a novel determinant of starch versus glycogen accumulation. We show that the phylogenies of GlgA2 and of 16S ribosomal RNA display significant congruence. This suggests that this enzyme evolved together with cyanobacteria when they diversified over 2 billion years ago. However, cyanobacteria can be ruled out as direct progenitors of the SSIII/SSIV ancestral gene found in Archaeplastida. Hence, both cyanobacteria and plants recruited similar enzymes independently to perform analogous tasks, further emphasizing the importance of convergent evolution in the appearance of starch from a preexisting glycogen metabolism network.Peer Reviewe

The SPIRAL radioactive ion beam facility

This document describes the scientific goals as well as the technical choices of the SPIRAL project (Système de Production d'Ions Radioactifs et d'Accélération en Ligne)

Morphology and structure of crystalline polysaccharides. Some recent studies

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Network formation in dilute amylose and amylopectin studied by TEM

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Orientation of native cellulose in an electric field

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Nanoscale measurement of stress and strain by quantitative high-resolution electron microscopy

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Stress and strain around grain-boundary dislocations measured by high-resolution electron microscopy

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Geometric phase analysis of lattice images from algal cellulose microfibrils

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B→A allomorphic transition in native starch and amylose spherocrystals monitored by in situ synchrotron X-ray diffraction

International audienceSingle crystals of amylose V2-propanol, i.e., amylose cocrystallized with water and 2-propanol, were prepared from synthetic linear amylose. When observed under frozen hydrated conditions, these crystals yielded base-plane electron diffraction diagrams containing more than 100 independent diffraction spots, whose intensities were used to solve the crystal structure of this complex. The molecular and crystal structure of amylose V2-propanol clearly indicated that the amylose molecules were organized in 7-fold left-handed helices, with 2-propanol and water molecules located as guests both within and between the helices. The V2-propanol unit cell contains four helices, distributed in two antiparallel pairs of parallel helices organized along the P212121 symmetry. The helices are organized along alternating motifs of four helices in a close-packed hexagonal arrangement together with four others in a nearly square organization surrounding a central column of water and 2-propanol. Whereas the location of the amylose helices is well established in the unit cell, the coordinates of the guest molecules could not be defined with certainty, most likely due to a positional disorder. A tentative model of the guest molecule distribution is presented, which consists of two 2-propanol and two water molecules within the helical cavity together with four water molecules and two 2-propanol molecules between the helices. The mobility of the guest and its description as a continuum, rather than at fixed crystallographic positions, explain why so many structures isomorphous to V2-propanol can be obtained with different guest molecules, while yielding similar electron diffraction diagrams