Development of New Targeted Inulin Complex Nanoaggregates for siRNA Delivery in Antitumor Therapy

Here, a novel strategy of formulating efficient polymeric carriers based on the already described INU-IMI-DETA for gene material whose structural, functional, and biological properties can be modulated and improved was successfully investigated. In particular, two novel derivatives of INU-IMI-DETA graft copolymer were synthesized by chemical functionalisation with epidermal growth factor (EGF) or polyethylenglycol (PEG), named INU-IMI-DETA-EGF and INU-IMI-DETA-PEG, respectively, in order to improve the performance of already described “inulin complex nanoaggregates” (ICONs). The latter were thus prepared by appropriately mixing the two copolymers, by varying each component from 0 to 100 wt% on the total mixture, named EP-ICONs. It was seen that the ability of the INU-IMI-DETA-EGF/INU-IMI-DETA-PEG polymeric mixture to complex siGL3 increases with the increase in the EGF-based component in the EP-ICONs and, for each sample, with the increase in the copolymer:siRNA weight ratio (R). On the other hand, the susceptibility of loaded siRNA towards RNase decreases with the increase in the pegylated component in the polymeric mixture. At all R values, the average size and the zeta potential values are suitable for escaping from the RES system and suitable for prolonged intravenous circulation. By means of biological characterisation, it was shown that MCF-7 cells are able to internalize mainly the siRNA-loaded into EGF-decorated complexes, with a significant difference from ICONs, confirming its targeting function. The targeting effect of EGF on EP-ICONs was further demonstrated by a competitive cell uptake study, i.e., after cell pre-treatment with EGF. Finally, it was shown that the complexes containing both EGF and PEG are capable of promoting the internalisation and therefore the transfection of siSUR, a siRNA acting against surviving mRNA, and to increase the sensitivity to an anticancer agent, such as doxorubicin.     

Nanoparticles based on novel amphiphilic polyaspartamide copolymers

In this article, the synthesis of two amphiphilic polyaspartamide copolymers, useful to obtain polymeric nanoparticles without using surfactants or stabilizing agents, is described. These copolymers were obtained starting from α,β-poly-(N-2-hydroxyethyl)-dl-aspartamide (PHEA) by following a novel synthetic strategy. In particular, PHEA and its pegylated derivative (PHEA-PEG₂₀₀₀) were functionalized with poly(lactic acid) (PLA) through 1,1′-carbonyldiimidazole (CDI) activation to obtain PHEA–PLA and PHEA-PEG₂₀₀₀–PLA graft copolymers, respectively. These copolymers were properly purified and characterized by ¹H-NMR, FT-IR, and Size Exclusion Chromatography (SEC) analyses, which confirmed that derivatization reactions occurred. Nanoparticles were obtained from PHEA–PLA and PHEA-PEG₂₀₀₀–PLA graft copolymers by using the high pressure homogenization-solvent evaporation method, avoiding the use of surfactants or stabilizing agents. Polymeric nanoparticles were characterized by dimensional analysis, before and after freeze-drying process, and Scanning Electron Microscopy (SEM). Zeta potential measurements and X-ray Photoelectron Spectroscopy (XPS) analysis demonstrated the presence of PEG and/or PHEA onto the PHEA-PEG₂₀₀₀–PLA and PHEA–PLA nanoparticle surface, respectively.     

Polyaspartamide–Polylactide Graft Copolymers with Tunable Properties for the Realization of Fluorescent Nanoparticles for Imaging

Here, the synthesis and the characterization of novel amphiphilic graft copolymers with tunable properties, useful in obtaining polymeric fluorescent nanoparticles for application in imaging, are described. These copolymers are obtained by chemical conjugation of rhodamine B (RhB) moieties, polylactic acid (PLA), and O‐(2‐aminoethyl)‐O′‐methyl poly(ethylene glycol) (PEG) on α,β‐poly(N‐2‐hydroxyethyl)‐d,l ‐aspartamide (PHEA). In particular, PHEA is first functionalized with RhB to obtain PHEA–RhB with a derivatization degree in RhB (DD_RhB) equal to 0.55 mol%. By varying the reaction conditions, different amounts of PLA are grafted on PHEA–RhB to obtain PHEA‐RhB‐PLA with DD_PLA equal to 1.9, 4.0, and 6.2 mol%. Then, PEG chains are grafted on PHEA‐RhB‐PLA derivatives to obtain PHEA‐RhB‐PLA‐PEG graft copolymers. The preparation of polymeric fluorescent nanoparticles with tunable properties and spherical shape is described by using PHEA‐RhB‐PLA‐PEG with DD in PLA and PEG equal to 4.0 and 4.9 mol%, by following easily scaling up processes, such as emulsion‐solvent evaporation and high pressure homogenization (HPH)‐solvent evaporation techniques.

     

The low-pressure focal plane detector of the MAGNEX spectrometer

The focal plane detector of the MAGNEX large acceptance magnetic spectrometer is presented. It is based on a large low-pressure gas-filled tracker followed by a wall of silicon detectors to stop the particles. It has been designed for the stringent requirements from the ion optics and the foreseen use with heavy ions. The performances of the device are demonstrated using 4MeV/u oxygen beams. The results of the tests are described and discussed in view of the application of the particle identification and trajectory reconstruction techniques to recover the kinematic properties of the reaction products. They demonstrate the suitability of such detector in a wide range of experiments where low-energy thresholds, large-accepted solid angle, precise momentum measurement and good particle identification are needed.     

Hydrogen Production by Steam Reforming of Ethanol: A Two Step Process

A two-layer fixed-bed catalytic reactor for hydrogen production by steam reforming of ethanol is proposed. In this reactor ethanol is first converted to acetaldehyde over a Cu-based catalyst and then acetaldehyde is converted to a hydrogen-rich mixture over a Ni-based catalyst. It is shown that the use of such type of reactor prevents coke formation and provides hydrogen yields closed to equilibrium.     

Oxidative chemical polymerization of pyrrole

A reaction calorimeter has been used to determine at three different temperatures the enthalpy values for the polymerization of pyrrole dissolved in acetonitrile, by using FeCl₃ as the oxidative agent. From the calorimetric data it has been found that the reaction is first-order with respect to the pyrrole. The rate constants at the same temperatures have also been determined. By using the Arrhenius equation we have obtained the activation energy for the formation of this electroconducting polymer.Financial support from the italian National Research Council (CNR) is gratefully acknowledged.     

Calorimetric investigation of the interaction between a macromolecular prodrug of diflunisal and human platelets

The thermal effect due to the interaction between human platelets and α,β poly(N-hydroxy-ethyl)-DL-aspartamide (PHEA) or the PHEA-Diflunisal conjugate was measured by the calorimetric technique at 25°C. The experimental data confirm that PHEA is a biocompatible macromolecule and that its conjugate influences the physiological activity of human platelets.     

Preparation and characterization of new hydrogels based on hyaluronic acid and α,β-polyaspartylhydrazide

Hyaluronic acid (HA) has been crosslinked with α,β-polyaspartylhydrazide (PAHy). The crosslinking reaction has been performed in acidic medium in the presence of various amounts of N-ethyl-N′-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC). All obtained samples have been characterized by FT-IR analysis and swelling measurements in double distilled water that have confirmed the occurrence of a chemical linkage between two polymers and the affinity towards aqueous medium of HA-PAHy networks, respectively.In vitro degradation assays have been performed in simulated physiological conditions as well as in the presence of hyaluronidase. Experimental data evidenced that HA-PAHy samples undergo a poor chemical and a reduced enzymatic degradation unlike native HA.