Scattering investigation of multiscale organization in aqueous solutions of native xanthan

The hierarchical morphology of xanthan solutions is analyzed by light and neutron scattering in a broad range of concentrations in order to connect their morphology to their well-documented dynamic properties. Static light scattering inside the semidilute regime is dominated by the form factor of individual xanthan chains while at higher concentrations chain interconnections appear to modify the low wave vector scattering. Dynamic light scattering reveals the self-similar nature of the solutions caused by interchain associations as intensity autocorrelation functions present power-law behaviour. Small angle neutron scattering is dominated by the fractal scattering from the formed network at intermediate length scales. At small length scales the rigid structure of xanthan is revealed and the molecular weight per unit length is extracted. No detectable morphological alterations for shear rates up to 1000 rad/s are observed revealing that the shear thinning behaviour of xanthan is related to the disruption of chain-chain associations

Micelles from HOOC-PnBA- b -PAA-C12_{12} H15_{15} Diblock Amphiphilic Polyelectrolytes as Protein Nanocarriers

We investigate the potential of self-assembled nanostructures of the PnBA-b-PAA amphiphilic diblock polyelectrolyte as candidates for protein nanocarriers. Three PnBA-b-PAA copolymers with different molecular weights and PnBA/PAA weight ratios are tested. The system with the most well-defined core–shell micellar structure is chosen for complexation with lysozyme. Its solutions are found to contain well-defined core–shell micelles that are stable upon increase in solution salt content to physiological levels. Upon mixing with lysozyme we find that the protein globules accumulate preferably at the outer parts of the hydrated corona of the micelles. Increasing the protein concentration, intermicellar aggregation is enhanced in a controllable way. At high salt content the number of proteins per micelle is lower compared with the low salt content, which points to an interaction of predominantly electrostatic nature. While light scattering is very sensitive to complexation, small-angle neutron scattering is able to distinguish between the contributions from individual micelles and aggregates. This work demonstrates the use of scattering techniques to characterize protein–polymer interactions in multiple hierarchical levels

Maleimide-functionalised PLGA-PEG nanoparticles as mucoadhesive carriers for intravesical drug delivery

Low permeability of the urinary bladder epithelium, poor retention of the chemotherapeutic agents due to dilution and periodic urine voiding as well as intermittent catheterisations are the major limitations of intravesical drug delivery used in the treatment of bladder cancer. In this work, maleimide-functionalised poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG-Mal) nanoparticles were developed. Their physicochemical characteristics, including morphology, architecture and molecular parameters have been investigated by means of dynamic light scattering, transmission electron microscopy and small-angle neutron scattering techniques. It was established that the size of nanoparticles was dependent on the solvent used in their preparation and molecular weight of PEG, for example, 105 ± 1 nm and 68 ± 1 nm particles were formed from PLGA20K-PEG5K in dimethyl sulfoxide and acetone, respectively. PLGA-PEG-Mal nanoparticles were explored as mucoadhesive formulations for drug delivery to the urinary bladder. The retention of fluorescein-loaded nanoparticles on freshly excised lamb bladder mucosa in vitro was evaluated and assessed using a flow-through fluorescence technique and Wash Out50 (WO50) quantitative method. PLGA-PEG-Mal nanoparticles (NPs) exhibited greater retention on urinary bladder mucosa (WO50 = 15 mL) compared to maleimide-free NPs (WO50 = 5 mL). The assessment of the biocompatibility of PEG-Mal using the slug mucosal irritation test revealed that these materials are non-irritant to mucosal surfaces

Structural characterization by scattering and spectroscopic methods and biological evaluation of polymeric micelles of poloxamines and TPGS as nanocarriers for miltefosine delivery

Miltefosine (MF), an alkylphospholipid originally developed for breast cancer treatment, is a highly active drug for the treatment against leishmaniasis, a neglected tropical disease considered the world’s second leading cause of death by a parasitic agent after malaria. MF exhibits dose-limiting gastrointestinal side effects in patients and its penetration through lipophilic barriers is reduced. In this work we propose a reformulation of MF by incorporating the drug to poly(ethylene)oxide (PEO)-based polymeric micelles, specifically, D-α-tocopheryl polyethylene glycol succinate (TPGS) and Tetronic block copolymers (T904 and T1107). A full structural characterization of the aggregates has been carried out by SANS (small-angle neutron scattering) and dynamic light scattering (DLS), in combination with proton 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, to determine the precise location of the drug. The structure of MF micelles has been characterized as a function of the temperature and concentration. In the presence of the block-copolymers, MF forms mixed micelles in a wide range of temperatures, TPGS being the co-surfactant that incorporates more MF unimers. The hydrophobic tail of MF and those of the block copolymers are in close contact within the micelles, which present a core-shell structure with a hydrophilic corona formed by the PEG blocks of the TPGS and the zwitterion head group of the MF. In order to identify the best carrier, the antileishmanicidal activity of MF in the different formulations has been tested on macrophages, promastigotes and intracellular amastigotes. The combination of the three vehicles with MF makes the formulated drug more active than MF alone against L. major promastigotes, however, only the combination with T904 increases the MF activity against intracellular amastigotes. With the aim of exploring gel-based formulations of the drug, the combination of MF and T1107 under gelation conditions has also been investigated.The authors gratefully acknowledge the financial support provided by MINECO (Project MAT2014-59116-C2), Obra Social La Caixa (LCF/PR/PR13/11080005), University Carlos III Strategic Action in Composites materials and interphases 2011/00287/002, Fundación Caja Navarra, Gobierno de Navarra-Salud (12/2017), Fundación Roviralta, Ubesol, Government of Navarre, Laser Ebro, Inversiones Garcilaso de la Vega and COST actions CA18217 and CA18218. JCNS is acknowledged for the access to the KWS-2 diffractometer at the Heinz Maier-Leibnitz Zentrum (MLZ), Garching, Germany. J.P-R. also acknowledges the Asociación de Amigos de la Universidad de Navarra for his doctoral grant. This work benefited from the use of the SasView application, originally developed under NSF award DMR-0520547. Sasview contains code developed with funding from the European Union's Horizon 2020 research and innovation program under the SINE2020 project, grant agreement No 654000

La multifonctionnalité de l'agriculture : un concept d'avenir ?

International audienceLa multifonctionnalité de l'agriculture : un concept d'avenir ? Etude par Luc Bodiguel chargé de recherche, UMR CNRS 3128, Droit et changement social (DCS)chargé d'enseignement à la faculté de droit de Nantes et d'Angers Accès au sommaire Comment comprendre aujourd'hui le concept de multifonctionnalité de l'agriculture ? Les réformes française et communautaire sont-elles venues lui donner un véritable contenu juridique ? Une autre portée politique ? Ou, au contraire, la multifonctionnalité de l'agriculture est-elle restée au stade théorique, au concept, voire, at -elle été dépassée par d'autres concepts plus influents, plus opérationnels ou plus à la mode ? Enfin, à quoi peut bien encore servir le concept de multifonctionnalité de l'agriculture d'un point de vue politique et juridique ? Afin de tenter de répondre à ces questions, Luc Bodiguel nous propose d'observer tout d'abord les fondements et règles de droit qui peuvent aujourd'hui être liés au concept de multifonctionnalité pour ensuite s'interroger sur l'avenir du concept au vu du droit français, communautaire et de l'organisation mondiale du commerce

Inner structure and dynamics of microgels with low and medium crosslinker content prepared via surfactant-free precipitation polymerization and continuous monomer feeding approach

The preparation of poly(N-isopropylacrylamide) microgels via classical precipitation polymerization (batch method) and a continuous monomer feeding approach (feeding method) leads to different internal crosslinker distributions, i.e., from core–shell-like to a more homogeneous one. The internal structure and dynamics of these microgels with low and medium crosslinker concentrations are studied with dynamic light scattering and small-angle neutron scattering in a wide q-range below and above the volume phase transition temperature. The influence of the preparation method, and crosslinker and initiator concentration on the internal structure of the microgels is investigated. In contrast to the classical conception where polymer microgels possess a core–shell structure with the averaged internal polymer density distribution within the core part, a detailed view of the internal inhomogeneities of the PNIPAM microgels and the presence of internal domains even above the volume phase transition temperature, when polymer microgels are in the deswollen state, are presented. The correlation between initiator concentration and the size of internal domains that appear inside the microgel with temperature increase is demonstrated. Moreover, the influence of internal inhomogeneities on the dynamics of the batch- and feeding-microgels studied with neutron spin-echo spectroscopy is reported.TU Berlin, Open-Access-Mittel - 201

Structure and domain dynamics of human lactoferrin in solution and the influence of Fe(III)-ion ligand binding

BackgroundHuman lactoferrin is an iron-binding protein of the innate immune system consisting of two connected lobes, each with a binding site located in a cleft. The clefts in each lobe undergo a hinge movement from open to close when Fe3+ is present in the solution and can be bound. The binding mechanism was assumed to relate on thermal domain fluctuations of the cleft domains prior to binding. We used Small Angle Neutron Scattering and Neutron Spin Echo Spectroscopy to determine the lactoferrin structure and domain dynamics in solution.ResultsWhen Fe3+ is present in solution interparticle interactions change from repulsive to attractive in conjunction with emerging metas aggregates, which are not observed without Fe3+. The protein form factor shows the expected change due to lobe closing if Fe3+ is present. The dominating motions of internal domain dynamics with relaxation times in the 30–50 ns range show strong bending and stretching modes with a steric suppressed torsion, but are almost independent of the cleft conformation. Thermally driven cleft closing motions of relevant amplitude are not observed if the cleft is open.ConclusionThe Fe3+ binding mechanism is not related to thermal equilibrium fluctuations closing the cleft. A likely explanation may be that upon entering the cleft the iron ion first binds weakly which destabilizes and softens the hinge region and enables large fluctuations that then close the cleft resulting in the final formation of the stable iron binding site and, at the same time, stable closed conformation