ALBERT

Notes: Injected, nano-scale drug delivery systems, or nanovectors, are ideal candidates toprovide breakthrough solutions to the time-honored problem of optimizing therapeutic index for atreatment. Even modest amounts of progress towards this goal have historically engenderedsubstantial benefits across multiple fields of medicine, with the translability, for example, fromoncology to infectious diseases being granted by the fact that the progresses had a single commondenominator in the underlying technological platform. In this work we combine multiscalemolecular modeling and experimental approaches to define the mode and the molecularrequirements of the interaction of oligonucleotide-based therapeutics (e.g., small interfering(si)RNA) and dendrimeric delivery reagents. In details, by mimicking in silico the experimentsperformed in vitro, information at the molecular level (e.g., interaction forces, mechanisms,structures, free energies of binding, self-assembly, etc.), which cannot be accessed by otherexperimental techniques, are obtained. Thus, critical molecular parameters for optimizing and denovo designing nanocargos for tissues and tumor specific uptake can be determined. This wouldprovide valuable information to devise optimal delivery modalities that would increase the efficacyof siRNA therapeutics in cells and laboratory animals and move them toward clinical applications

Notes: Transport and surface interactions of proteins in nanopore membranes play a key role inmany processes of biomedical importance. Although the use of porous materials provides a largesurface-to-volume ratio, the efficiency of the operations is often determined by transport behavior,and this is complicated by the fact that transport paths (i.e., the pores) are frequently of moleculardimensions. Under these conditions, wall effects become significant, with the mobility of moleculesbeing affected by hydrodynamic interactions between protein molecules and the wall. Modeling oftransport in pores is normally carried out at the continuum level, making use of such parameters ashindrance coefficients; these in turn are typically estimated using continuum methods applied at thelevel of individual diffusing particles. In this work we coupled experimental evidences to manyscalemolecular simulations for the analysis of hen egg-white lysozyme adsorption/diffusionthrough a microfabricated silicon membrane, having pores of nanometric size in only onedimension. Our joint efforts allowed us a) to elucidate the specific mechanisms of interactionbetween the biopolymer and the silicon surface, and b) to derive molecular energetic and structuralparameters to be employed in the formulation of a mathematical model of diffusion, thus filling thegap between the nano- and the macroscale

Notes: Industrial scraps cannot be reused in an advantageous way, mainly because of theirdegradation. When possible, rejects are added to the virgin material for new molding, although theamount of recycled block copolymer cannot exceed 15% of moldable material to obtain good finalperformances. The remaining amount of scraps then follows three different routes: i) employment invery poor applications, ii) land filling, and iii) thermal treatment. For this reason, post industrialrejects constitute a major problem both from the standpoint of the European legislation and policy,and from the economic side where enterprises are concerned. In this work we have applied amultiscale simulation approach to study the nanostructured equilibrium morphology of blendsconsisting of mainly recycled block copolymers of special interest in the automotive industry. Themain goal was the definition of the possible causes leading to incompatibility due to non virginmaterials. In particular, starting from atomistic-based simulations we derived a procedure to 1)describe in appropriate fashion the polymer chains in terms of the relevant Gaussian models, and 2)determine the relevant Flory-Huggins interaction parameters. Finally, we coupled mesoscale modelwith finite elements codes to obtain a quantified structure-property relationship for mechanicalmodulus and coefficient of thermal expansion

Notes: A current challenge of physical, chemical and engineering sciences is to developtheoretical tools for predicting structure and physical properties of hybrid organic inorganicnanocomposite from the knowledge of a few input parameters. However, despite all efforts,progress in the prediction of macroscopic physical properties from structure has been slow. Majordifficulties relate to the fact that (a) the microstructural elements in multiphase material are notshaped or oriented as in the idealizations of computer simulations, and more than one type cancoexist; (b) multiple length and time scales are generally involved and must be taken into account,when overall thermodynamic and mechanical properties wish to be determined, and finally (c) theeffect of the interphases/interfaces on the physical properties is often not well understood andcharacterized. As a consequence, their role is often neglected in the development of new theoreticaltools or they are treated in a very empirical way. In this work, we focused on issues (b) and (c) in amultiscale molecular simulation framework, with the ultimate goal of developing acomputationally-based nanocomposite designing tool. In particular, we developed a hierarchicalprocedure in which lower scale (i.e., QM, MD and /or MC) simulations are performed to obtainparameters for higher scale (i.e., mesoscopic and/or finite element) calculations, from which thebulk properties of the hybrid nanocomposite material can be ultimately estimated

Notes: Abstract Many industrial products often include in their formulation more than one polysaccharide to achieve the desired properties during and after processing. Many such mixed systems behave as would be expected from the known properties of the individual polymers. In others, however, their properties are superior to those of either component alone, or may be qualitatively different. In many polysaccharide systems, the combination of a gelling polymer with a nongelling one gives rise to strong synergistic effects, as a consequence of interaction among different chain polymers and formation of mixed junction zones. Probably, the most exploited mixed gels, especially by the food industry, are those involving the microbial polysaccharide xanthan gum (XG) and the plant galactomannans, like locust bean gum (LBG). Concentrated aqueous systems of LBG and XG display quite different rheological properties: the former show the behaviour typical of hyperentangled macromolecular solutions, whereas the flow and viscoelastic properties of XG systems correspond to those of tenuous, weak-gel networks. Interestingly, when mixed together these macromolecules interact to form a firm, thermoreversible gel with synergistic effects. In the present paper we report the results of a thorough investigation of both polymer concentration and temperature effects on the rheological properties of mixed LBG-XG systems in 20 mM KCl under continuous and oscillatory flow conditions. Under continuous shear at 25°C, pure LBG shows the flow properties of a macromolecular solution, with a shear-thinning behaviour and a Newtonian region at low shear rates, whereas the rheological behaviour of XG and all LX mixed systems is that typical of weak-gels. Furthermore, in the mixed systems the viscosity values do not increase monotonically with increasing xanthan concentration, but the synergistic effect has a maximum in accordance with the XG:LBG ratio 1:1. As the temperature is increased from 25°C to 85°C, whilst the LBG system do not show any qualitative change but there is only a parallel, downward shift of viscosity values, in the case of xanthan there is a dramatic change in the corresponding curve profiles, due to the thermally induced helix-coil conformational transition. The differences in the rheological behaviour of the systems examined can be better shown through dynamic tests at 25°C. The strain sweeps performed at constant frequency of oscillation reveal that the mixed systems show higher sensitivity to strain amplitude, and lower strain values must be attained to ensure linear viscoelastic properties. The mechanical spectra clearly show the influence of composition on the viscoelastic properties of these biopolymer systems. All LX systems show the mechanical spectra typical of polysaccharide gels: G′ is always much greater than G″ and is nearly independent of the applied frequency over a wide frequency range. In addition, the marked gap between the elastic responses of the pure LBG and the LX 1:3 systems demonstrates the strong effect of the initial addition of xanthan to the pure LBG, especially in the low frequency range, whereas the highest synergistic effect is attained for the LX 1:1 system. A comprehensive description of the frequency dependence of both moduli can be suitably obtained through the four-parameter Friedrich model, which belongs to the class of fractional derivative approaches viscoelasticity. The same thermal effect is observed for the XG and all LX mixed systems considered, indicating a progressive change from the behaviour of a typical gel to that of a quasi-solution state, when temperature is increased from 25°C to 85°C. Among all mixed systems, the LX 1:1 has the highest values of the moduli at any temperature considered, and is characterized by the highest gel-sol transition temperature. In all LX systems, the temperature sweeps show that the gel-sol transition follows a two-step process, characterized by the presence of two inflection points in the relevant G* vs T curves. The first step could be reasonably ascribed to the melting process of the mixed xanthan-locust bean gum junction zones, in which the association of XG with LBG is occurring with the xanthan component in its fully ordered helical conformation. The second step, occurring at higher temperature, can be attributed to the conformational transition of the xanthan chains.

Notes: Homogeneous networks of an ionic polysaccharide (namely pectate) in the presence of divalent ions were prepared in situ by proper procedure and the kinetics of the gel formation was studied by means of a coaxial cylinder rheometer in oscillatory flow conditions. The stress response was expanded in a Fourier series and the variation of the components of the fundamental harmonic with time during the gelation process were examined. A model is proposed for the correlation between kinetic parameters such as the concentration of the species active during the gel formation and the rheological parameters that can be experimentally determined, like G′ and G′′. Considerations are developed concerning the mechanism that governs the gelation process under dynamic conditions.

Notes: The rheological behavior of carboxymethyl starch aqueous systems has been studied under continuous and oscillatory shear conditions. The systems examined exhibited shear-dependent properties, typical of dispersions having a weak degree of particle aggregation. A transition in the rheological properties was observed with increasing concentration and/or decreasing temperature, as a consequence of formation of a three-dimensional continuous network in the disperse phase under rest conditions. The shear-dependent behavior changed from shear-thinning to plastic and a finite plateau appeared in the low frequency region of mechanical spectra. A rheological model was proposed for the correlation of both shear-thinning and plastic data, thus making possible an objective definition of the rheological transition. Oscillatory flow data confirmed the results obtained in continuous shear conditions, that is, the frequency dependence of the complex viscosity was almost parallel to the dependence of the steady shear viscosity on the rate of shear. Moreover, the high strain sensitivity of the viscoelastic quantities and their analysis in terms of relaxation spectra clearly indicated the moderate degree of connectivity of the structural network. © 1992 John Wiley & Sons, Inc.