Green and cost-effective synthesis of copper nanoparticles by extracts of non-edible and waste plant materials from Vaccinium species: Characterization and antimicrobial activity.

The aim of this work was the green synthesis of copper nanoparticles (Cu-NPs) using aqueous extracts of (i) bilberry (Vaccinium myrtillus L.) waste residues from the production of fruit juices and (ii) non-edible "false bilberry" fruits (Vaccinium uliginosum L. subsp. gaultherioides). Different cupric salts (CuCl2, Cu(CH3COO)2 and Cu(NO3)2) were used for the synthesis. The formation of stable nanoparticles (CuNPs) was assessed by transmission electron microscopy and the oxidation state of copper in these aggregates was followed by X-ray photoelectron spectroscopy. The polyphenol composition of the extracts was characterized, before and after the synthesis, using spectrophotometric methods (i.e. total soluble polyphenols and total monomeric anthocyanins) and high-performance liquid chromatography coupled with tandem mass spectrometry (i.e. individual anthocyanins). Polyphenol concentration in the extracts was found to decrease after the synthesis, indicating their active participation to the processes, which led to the formation of Cu-NPs. The antimicrobial activity of Cu-NPs, berry extracts, and cupric ion solutions were analysed by broth microdilution and time-kill assays, on prokaryotic and eukaryotic models. The antimicrobial activity of Cu-NPs, especially those derived from bilberry waste residues, appeared to be higher for both Gram-negative and Gram-positive bacteria, and for fungi, compared to the ones of its single components (cupric salts and berry extracts). Therefore, Cu-NPs from the green synthesis here proposed can be considered as a cost-effective sanitization tool with a wide spectrum of action.

Antibiotic delivery by liposomes from prokaryotic microorganisms: Similia cum similis works better.

To date the effectiveness of antibiotics is undermined by microbial resistance, threatening public health worldwide. Enhancing the efficacy of the current antibiotic arsenal is an alternative strategy. The administration of antimicrobials encapsulated in nanocarriers, such as liposomes, is considered a viable option, though with some drawbacks related to limited affinity between conventional liposomes and bacterial membranes. Here we propose a novel "top-down" procedure to prepare unconventional liposomes from the membranes of prokaryotes (PD-liposomes). These vectors, being obtained from bacteria with limited growth requirements, also represent low-cost systems for scalable biotechnology production. In depth physico-chemical characterization, carried out with dynamic light scattering (DLS) and Small Angle X-ray Scattering (SAXS), indicated that PD-liposomes can be suitable for the employment as antibiotic vectors. Specifically, DLS showed that the mean diameter of loaded liposomes was ∼200-300nm, while SAXS showed that the structure was similar to conventional liposomes, thus allowing a direct comparison with more standard liposomal formulations. Compared to free penicillin G, PD-liposomes loaded with penicillin G showed minimal inhibitory concentrations against E. coli that were up to 16-times lower. Noteworthy, the extent of the bacterial growth inhibition was found to depend on the microorganisms from which liposomes were derived.

Boron as a platform for new drug design.

INTRODUCTION: Boron lies on the borderline between metals and non-metals in the periodic table. As such, it possesses peculiarities which render it suitable for a variety of applications in chemistry, technology and medicine. However, boron's peculiarities have been exploited only partially so far. AREAS COVERED: In this review, the authors highlight selected areas of research which have witnessed new uses of boron compounds in recent times. The examples reported illustrate how difficulties in the synthesis and physicochemical characterization of boronated molecules, encountered in past years, can be overcome with positive effects in different fields. EXPERT OPINION: Many potentialities of boron-based systems reside in the peculiar properties of both boron atoms (the ability to replace carbon atoms, electron deficiency) and of boronated compounds (hydrophobicity, lipophilicity, versatile stereochemistry). Taken in conjunction, these properties can provide innovative drugs. The authors highlight the need to further investigate the assembly of boronated compounds, in terms of drug design, since the mechanisms required to obtain supramolecular structures may be unconventional compared with the more standard molecules used. Furthermore, the authors propose that computational methods are a valuable tool for assessing the role of multicenter, quasi-aromatic bonds and its peculiar geometries.

Using liposomes as carriers for polyphenolic compounds: the case of trans-resveratrol.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol found in various plants, especially in the skin of red grapes. The effect of resveratrol on human health is the topic of numerous studies. In fact this molecule has shown anti-cancer, anti-inflammatory, blood-sugar-lowering ability and beneficial cardiovascular effects. However, for many polyphenol compounds of natural origin bioavailability is limited by low solubility in biological fluids, as well as by rapid metabolization in vivo. Therefore, appropriate carriers are required to obtain efficient therapeutics along with low administration doses.Liposomes are excellent candidates for drug delivery purposes, due to their biocompatibility, wide choice of physico-chemical properties and easy preparation.In this paper liposome formulations made by a saturated phosphatidyl-choline (DPPC) and cholesterol (or its positively charged derivative DC-CHOL) were chosen to optimize the loading of a rigid hydrophobic molecule such as resveratrol.Plain and resveratrol loaded liposomes were characterized for size, surface charge and structural details by complementary techniques, i.e. Dynamic Light Scattering (DLS), Zeta potential and Small Angle X-ray Scattering (SAXS). Nuclear and Electron Spin magnetic resonances (NMR and ESR, respectively) were also used to gain information at the molecular scale.The obtained results allowed to give an account of loaded liposomes in which resveratrol interacted with the bilayer, being more deeply inserted in cationic liposomes than in zwitterionic liposomes. Relevant properties such as the mean size and the presence of oligolamellar structures were influenced by the loading of RESV guest molecules.The toxicity of all these systems was tested on stabilized cell lines (mouse fibroblast NIH-3T3 and human astrocytes U373-MG), showing that cell viability was not affected by the administration of liposomial resveratrol.

Carbonic anhydrase inhibitors: design of spin-labeled sulfonamides incorporating TEMPO moieties as probes for cytosolic or transmembrane isozymes.

A series of spin-labeled sulfonamides incorporating TEMPO moieties were synthesized by a procedure involving the formation of a thiourea functionality between the benzenesulfonamide and free radical fragment of the molecules. The new compounds were tested as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and showed efficient inhibition of the physiologically relevant isozymes hCA II and hCA IX (hCA IX being predominantly found in tumors) and moderate to weak inhibitory activity against hCA I. Some derivatives were also selective for inhibiting the tumor-associated isoform over the cytosolic one CA II, and presented significant changes in their ESR signals when complexed to the enzyme active site, being interesting candidates for the investigation of hypoxic tumors overexpressing CA IX by ESR techniques, as well as for imaging/treatment purposes.