Effect of the polymer nature on the structural organization of lipid/polymer particle assemblies

The nano-organized LipoParticle assemblies, consisting of polymer particles coated with lipid layers, are investigated with the aim of evidencing the impact of the particle chemical nature on their physicochemical behavior. To this end, these colloidal systems are elaborated from anionic submicrometer poly(styrene) (P(St)) or poly(lactic acid) (PLA) particles, and lipid mixtures composed of zwitterionic 1,2-dipalmitoyl- sn-glycero-3-phosphocholine (DPPC) and cationic 1,2-dipalmitoyl-3-trimethylammonium-propane (DPTAP). As revealed by various experimental techniques, such as quasielastic light scattering, zeta potential measurements, transmission electron microscopy, and 1H NMR spectroscopy, the features of both LipoParticle systems are similar when cationic lipid formulations (DPPC/DPTAP mixtures) are used. This result emphasizes the major role of electrostatic interactions as driving forces in the assembly elaboration process. Conversely, the assemblies prepared only with the zwitterionic DPPC lipid are strongly dependent on the particle chemical nature. The structural characteristics of the assemblies based on PLA particles are not controlled and correspond to aggregates, contrary to P(St) particles. To understand this specific phenomenon, and to consequently improve the final organization of these assemblies which are potentially of great interest in biotechnology and biomedicine, numerous investigations are carried out such as the studies of the impact of the ionic strength and the pH of the preparation media, as well as the presence of ethanol (involved in the PLA particle synthesis) or the mean size of the lipid vesicles. From the resulting data and according to the nature of spherical solid support, hydrophobic effects, hydrogen bonds, or dipole-dipole interactions would also appear to influence the LipoParticle elaboration in the case of zwitterionic lipid formulation.     

Synthesis of oily core‐hybrid shell nanocapsules through interfacial free radical copolymerization in miniemulsion: Droplet formation and nucleation

Nanocapsules with an oily core and an organic/inorganic hybrid shell were elaborated by miniemulsion (co)polymerization of styrene, divinylbenzene, γ‐methacryloyloxy propyl trimethoxysilane, and N‐isopropyl acrylamide. The hybrid copolymer shell membrane was formed by polymerization‐induced phase separation at the interface of the oily nanodroplets with water. It was shown that the size, size distribution, and colloidal stability of the miniemulsion droplets were extremely dependent on the nature of the oil phase, the monomer content and the surfactant concentration. The less water‐soluble the hydrocarbon template and the higher the monomer content, the better the droplet stability. The successful formation of nanocapsules with the targeted core‐shell morphology (i.e., a liquid core surrounded by a solid shell) was evidenced by cryogenic transmission electron microscopy. Both nanocapsules and nanoparticles were produced by polymerization of the miniemulsion droplets. The proportion of nanoparticles increased with increasing monomer concentration in the oil phase. These undesirable nanoparticles were presumably formed by homogeneous nucleation as we showed that micellar nucleation could be neglected under our experimental conditions even for high surfactant concentrations. The introduction of γ‐methacryloyloxy propyl trimethoxysilane was considered to be the main reason for homogeneous nucleation. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 593–603, 2010     

Surface modification of cellulose microfibrils by periodate oxidation and subsequent reductive amination with benzylamine: a topochemical study

Never-dried sulfite wood pulp was beaten and subsequently microfibrillated before being submitted to periodate oxidation for various times. The oxidation progress, which was followed by ¹³C solid-state NMR spectroscopy in conjunction with degree of oxidation (DO) measurements together with ultrastructural observations, revealed that the cellulose crystallinity and microfibrillar integrity were kept intact until a DO of 0.3/0.4, indicating that at that level, the cellulose microfibrils had been oxidized exclusively at their surface. Beyond this DO value, the sample crystallinity started to deteriorate, as the oxidation progressed toward the core of the microfibrils. Remarkably, throughout the oxidation, the created carbonyl moieties were never observed, as they were readily recombined into hemiacetals by cyclization either within the same anhydro glucose unit (AGU) or with the adjacent un-oxidized AGUs of the same cellulose chain. At DO below 0.3/0.4, hemiacetal coupling with adjacent cellulose chains was also considered, but it appeared unlikely in view of the interchain distance imposed by the crystalline lattice. The oxidized samples were subjected to a reductive amination with benzylamine in order to convert their hydrophilic surfaces into hydrophobic ones. Despite the ease of this derivatization, the analysis of the ¹³C solid-state NMR spectra of the aminated products showed that, below a DO of 0.3, only half of the hemiacetal moieties could be converted into secondary amine products, whereas the other half remained untouched, likely for steric reasons.     

Characterization of hyperbranched glycopolymers produced in vitro using enzymes

Asymmetrical flow field flow fractionation (AF4) has proven to be a very powerful and quantitative method for the determination of the macromolecular structure of high molar mass branched biopolymers, when coupled with multi-angle laser light scattering (MALLS). This work describes a detailed investigation of the macromolecular structure of native glycogens and hyperbranched α-glucans (HBPs), with average molar mass ranging from 2?×?10⁶ to 4.3?×?10⁷ g mol^?1, which are not well fractionated by means of classical size-exclusion chromatography. HBPs were enzymatically produced from sucrose by the tandem action of an amylosucrase and a branching enzyme mimicking in vitro the elongation and branching steps involved in glycogen biosynthesis. Size and molar mass distributions were studied by AF4, coupled with online quasi-elastic light scattering (QELS) and transmission electron microscopy. AF4-MALLS-QELS has shown a remarkable agreement between hydrodynamic radii obtained by online QELS and by AF4 theory in normal mode with constant cross flow. Molar mass, size, and dispersity were shown to significantly increase with initial sucrose concentration, and to decrease when the branching enzyme activity increases. Several populations with different size range were observed: the amount of small size molecules decreasing with increasing sucrose concentration. The spherical and dense global conformation thus highlighted was partly similar to native glycogens. A more detailed study of HBPs synthesized from low and high initial sucrose concentrations was performed using complementary enzymatic hydrolysis of external chains and chromatography. It emphasized a more homogeneous branching pattern than native glycogens with a denser core and shorter external chains.

A mathematical model of aging-related and cortisol induced hippocampal dysfunction

Background  

The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD), the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silicomodel of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML). We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated.