Papers by Author: Sabrina Pricl

Abstract: Injected, nano-scale drug delivery systems, or nanovectors, are ideal candidates to provide breakthrough solutions to the time-honored problem of optimizing therapeutic index for a treatment. Even modest amounts of progress towards this goal have historically engendered substantial benefits across multiple fields of medicine, with the translability, for example, from oncology to infectious diseases being granted by the fact that the progresses had a single common denominator in the underlying technological platform. In this work we combine multiscale molecular modeling and experimental approaches to define the mode and the molecular requirements of the interaction of oligonucleotide-based therapeutics (e.g., small interfering (si)RNA) and dendrimeric delivery reagents. In details, by mimicking in silico the experiments performed 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 other experimental techniques, are obtained. Thus, critical molecular parameters for optimizing and de novo designing nanocargos for tissues and tumor specific uptake can be determined. This would provide valuable information to devise optimal delivery modalities that would increase the efficacy of siRNA therapeutics in cells and laboratory animals and move them toward clinical applications.

Abstract: A current challenge of physical, chemical and engineering sciences is to develop theoretical tools for predicting structure and physical properties of hybrid organic inorganic nanocomposite 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. Major difficulties relate to the fact that (a) the microstructural elements in multiphase material are not shaped or oriented as in the idealizations of computer simulations, and more than one type can coexist; (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) the effect of the interphases/interfaces on the physical properties is often not well understood and characterized. As a consequence, their role is often neglected in the development of new theoretical tools or they are treated in a very empirical way. In this work, we focused on issues (b) and (c) in a multiscale molecular simulation framework, with the ultimate goal of developing a computationally-based nanocomposite designing tool. In particular, we developed a hierarchical procedure in which lower scale (i.e., QM, MD and /or MC) simulations are performed to obtain parameters for higher scale (i.e., mesoscopic and/or finite element) calculations, from which the bulk properties of the hybrid nanocomposite material can be ultimately estimated.

Abstract: Transport and surface interactions of proteins in nanopore membranes play a key role in many processes of biomedical importance. Although the use of porous materials provides a large surface-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 molecular dimensions. Under these conditions, wall effects become significant, with the mobility of molecules being affected by hydrodynamic interactions between protein molecules and the wall. Modeling of transport in pores is normally carried out at the continuum level, making use of such parameters as hindrance coefficients; these in turn are typically estimated using continuum methods applied at the level of individual diffusing particles. In this work we coupled experimental evidences to manyscale molecular simulations for the analysis of hen egg-white lysozyme adsorption/diffusion through a microfabricated silicon membrane, having pores of nanometric size in only one dimension. Our joint efforts allowed us a) to elucidate the specific mechanisms of interaction between the biopolymer and the silicon surface, and b) to derive molecular energetic and structural parameters to be employed in the formulation of a mathematical model of diffusion, thus filling the gap between the nano- and the macroscale.

Abstract: Industrial scraps cannot be reused in an advantageous way, mainly because of their degradation. When possible, rejects are added to the virgin material for new molding, although the amount of recycled block copolymer cannot exceed 15% of moldable material to obtain good final performances. The remaining amount of scraps then follows three different routes: i) employment in very poor applications, ii) land filling, and iii) thermal treatment. For this reason, post industrial rejects 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 a multiscale simulation approach to study the nanostructured equilibrium morphology of blends consisting of mainly recycled block copolymers of special interest in the automotive industry. The main goal was the definition of the possible causes leading to incompatibility due to non virgin materials. 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 model with finite elements codes to obtain a quantified structure-property relationship for mechanical modulus and coefficient of thermal expansion.