Mariangela Bellusci

Antibiotic delivery polyurethanes containing albumin and polyallylamine nanoparticles

Nano-structured polymers delivering an antibiotic for the prevention of medical device-related infections were developed. Systems consisted of bovine serum albumin or polyallylamine nanoparticles alone or entrapped in a polyurethane and then loaded with cefamandole nafate, chosen as a drug model. Results showed that nanoparticles alone were able to adsorb high antibiotic amounts due to their high surface/volume ratio. However, they released cefamandole in an uncontrolled fashion, leading to a rapid loss of antibacterial activity. Improvements in the release control were obtained when CEF loaded and non-loaded nanoparticles were entrapped in a carboxylated polyurethane. For these systems the drug delivery was at least of 50% with respect to nanoparticles alone with a prolonged antimicrobial activity up to 9 days.

Biodistribution and acute toxicity of a nanofluid containing manganese iron oxide nanoparticles produced by a mechanochemical process

Superparamagnetic iron oxide nanoparticles are candidate contrast agents for magnetic resonance imaging and targeted drug delivery. Biodistribution and toxicity assessment are critical for the development of nanoparticle-based drugs, because of nanoparticle-enhanced biological reactivity. Here, we investigated the uptake, in vivo biodistribution, and in vitro and in vivo potential toxicity of manganese ferrite (MnFe2O4) nanoparticles, synthesized by an original high-yield, low-cost mechanochemical process. Cultures of murine Balb/3T3 fibroblasts were exposed for 24, 48, or 72 hours to increasing ferrofluid concentrations. Nanoparticle cellular uptake was assessed by flow-cytometry scatter-light measurements and microscopy imaging after Prussian blue staining; cytotoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony-forming assays. After a single intravenous injection, in vivo nanoparticle biodistribution and clearance were evaluated in mice by Mn spectrophotometric determination and Prussian blue staining in the liver, kidneys, spleen, and brain at different posttreatment times up to 21 days. The same organs were analyzed for any possible histopathological change. The in vitro study demonstrated dose-dependent nanoparticle uptake and statistically significant cytotoxic effects from a concentration of 50 μg/mL for the MTT assay and 20 μg/mL for the colony-forming assay. Significant increases in Mn concentrations were detected in all analyzed organs, peaking at 6 hours after injection and then gradually declining. Clearance appeared complete at 7 days in the kidneys, spleen, and brain, whereas in the liver Mn levels remained statistically higher than in vehicle-treated mice up to 3 weeks postinjection. No evidence of irreversible histopathological damage to any of the tested organs was observed. A comparison of the lowest in vitro toxic concentration with the intravenously injected dose and the administered dose of other ferrofluid drugs currently in clinical practice suggests that there might be sufficient safety margins for further development of our formulation.

Design and characterization of antimicrobial usnic acid loaded-core/shell magnetic nanoparticles

The application of magnetic nanoparticles (MNPs) in medicine is considered much promising especially because they can be handled and directed to specific body sites by external magnetic fields. MNPs have been investigated in magnetic resonance imaging, hyperthermia and drug targeting. In this study, properly functionalized core/shell MNPs with antimicrobial properties were developed to be used for the prevention and treatment of medical device-related infections. Particularly, surface-engineered manganese iron oxide MNPs, produced by a micro-emulsion method, were coated with two different polymers and loaded with usnic acid (UA), a dibenzofuran natural extract possessing antimicrobial activity. Between the two polymer coatings, the one based on an intrinsically antimicrobial cationic polyacrylamide (pAcDED) resulted to be able to provide MNPs with proper magnetic properties and basic groups for UA loading. Thanks to the establishment of acid-base interactions, pAcDED-coated MNPs were able to load and release significant drug amounts resulting in good antimicrobial properties versus Staphylococcus epidermidis (MIC = 0.1 mg/mL). The use of pAcDED having intrinsic antimicrobial activity as MNP coating in combination with UA likely contributed to obtain an enhanced antimicrobial effect. The developed drug-loaded MNPs could be injected in the patient soon after device implantation to prevent biofilm formation, or, later, in presence of signs of infection to treat the biofilm grown on the device surfaces.

Lipase Immobilization on Differently Functionalized Vinyl-Based Amphiphilic Polymers: Influence of Phase Segregation on the Enzyme Hydrolytic Activity

Microbial lipase from Candida rugosa was immobilized by physical adsorption onto an ethylene-vinyl alcohol polymer (EVAL) functionalized with acyl chlorides. To evaluate the influence of the reagent chain-length on the amount and activity of immobilized lipase, three differently long aliphatic fatty acids were employed (C8, C12, C18), obtaining EVAL functionalization degrees ranging from 5% to 65%. The enzyme-polymer affinity increased with both the length of the alkyl chain and the matrix hydrophobicity. In particular, the esterified polymers showed a tendency to give segregated hydrophilic and hydrophobic domains. It was observed the formation of an enzyme multilayer at both low and high protein concentrations. Desorption experiments showed that Candida rugosa lipase may be adsorbed in a closed form on the polymer hydrophilic domains and in an open, active structure on the hydrophobic ones. The best results were found for the EVAL-C18 13% matrix that showed hyperactivation with both the soluble and unsoluble substrate after enzyme desorption. In addition, this supported biocatalyst retained its activity for repetitive cycles.

Reactive Pellets for Improved Solar Hydrogen Production Based on Sodium Manganese Ferrite Thermochemical Cycle

Hydrogen production by water-splitting thermochemical cycle based on manganese ferrite/sodium carbonate reactive system is reported. Two different preparation procedures for manganese ferrite/sodium carbonate mixture were adopted and compared in terms of material capability to cyclical hydrogen production. According to the first procedure, conventionally synthesized manganese ferrite, i.e., high temperature (1250°C) heating in Ar of carbonate/oxide precursors, was mixed with sodium carbonate. The blend was tested inside a temperature programed desorption reactor using a cyclical hydrogen production/material regeneration scheme. After a few cycles, the mixture resulted rapidly passivated and unable to further produce hydrogen. An innovative method that avoids the high temperature synthesis of manganese ferrite is presented. This procedure consists in a set of consecutive thermal treatments of a manganese carbonatel sodium carbonateliron oxide mixture in different environments (inert, oxidative, and reducing) at temperatures not exceeding 750°C. Such material, whose observed chemical composition consists of manganese ferrite and sodium carbonate in stoichiometric amounts, is able to evolve hydrogen during 25 consecutive water-splitting cycles, with a small decrease in cyclical production efficiency.

Progress in Understanding Factors Governing the Sodium Manganese Ferrite Thermochemical Cycle

The mixed sodium manganese ferrite thermochemical cycle for sustainable hydrogen production is reviewed. Both the hydrogen production step and the reaction that leads to the regeneration of initial reactants are described as multistep reactions. The chemical cyclability of the reactive system has been demonstrated at 750°C.

Magnetic Metal–Organic Framework Composite by Fast and Facile Mechanochemical Process

Magnetic porous metal-organic framework nanocomposite was obtained by an easy, efficient, and environmentally friendly fabrication method. The material consists in magnetic spinel iron oxide nanoparticles incorporated in an iron(III) carboxylate framework. The magnetic composite was fabricated by a multistep mechanochemical approach. In the first step, iron oxide nanoparticles were obtained via ball milling inducing mechanochemical reaction between iron chlorides and NaOH using NaCl as dispersing agent. Magnetic nanoparticles (MNs) were functionalized by neat grinding with benzene-1,3,5-tricarboxylic acid (1, 3, 5 BTC) and were then subjected to liquid assisted milling using hydrated FeCl3, water, and ethanol to obtain a magnetic framework composite (MFC) consisting of iron oxide nanoparticles encapsulated in a MOF matrix. We report, for the first time, the applicability of the grinding method to obtain a magnetic composite of metal-organic frameworks. The synthesized material exhibits magnetic characteristics and high porosity, and it has been tested as carrier for targeted drug delivery studying loading and release of a model drug (doxorubicin). Developed systems can associate therapeutics and diagnostics properties with possible relevant impact for theranostic and personalized patient treatment. Furthermore, the material properties make them excellent candidates for several other applications such as catalysis, sensing, and selective sequestration processes.

Optimized reactants mixture and products hydrolysis in the manganese oxide thermochemical cycle

A novel system composed by an aqueous slurry prepared by MnO and NaOH mixture was tested for the hydrogen production in the sodium manganese oxide thermochemical cycle. The hydrogen evolution occurs at lower temperature than conventional mixtures utilized in the cycle. Experiments performed in a Temperature Programmed Desorption/Reaction apparatus (TPD/TPR) have evidenced hydrogen production around 500°C. The hydrolysis step of α-NaMnO2 has been studied and the importance to conduct hydrolysis reaction under inert gas is discussed. A manganese disproportion mechanism is hypothesized to explain the appearance of manganese (II) and manganese (IV) containing phases.Copyright