Green Solid Lipid Nanoparticles by Fatty Acid Coacervation: An Innovative Nasal Delivery Tool for Drugs Targeting Cerebrovascular and Neurological Diseases.

Cerebrovascular and neurological diseases are characterized by neuroinflammation, which alters the neurovascular unit, whose interaction with the choroid plexus is critical for maintaining brain homeostasis and producing cerebrospinal fluid. Dysfunctions in such process can lead to conditions such as idiopathic normal pressure hydrocephalus, a common disease in older adults. Potential pharmacological treatments, based upon intranasal administration, are worthy of investigation because they might improve symptoms and avoid surgery by overcoming the blood-brain barrier and avoiding hepatic metabolism. Nasal lipid nanocarriers, such as solid lipid nanoparticles, may increase the nasal retention and permeation of drugs. To this aim, green solid lipid nanoparticles, obtained by coacervation from natural soaps, are promising vehicles due to their specific lipid matrix composition and the unsaponifiable fraction, endowed with antioxidant and anti-inflammatory properties, and thus suitable for restoring the neurovascular unit function. In this experimental work, such green solid lipid nanoparticles, fully characterized from a physico-chemical standpoint, were loaded with a drug combination suitable for reverting hydrocephalus symptoms, allowing us to obtain a non-toxic formulation, a reduction in the production of the cerebrospinal fluid in vitro, and a vasoprotective effect on an isolated vessel model. The pharmacokinetics and biodistribution of fluorescently labelled nanoparticles were also tested in animal models.

Cell Membrane Fragment-Wrapped Parenteral Nanoemulsions: A New Drug Delivery Tool to Target Gliomas.

Poor prognosis in high-grade gliomas is mainly due to fatal relapse after surgical resection in the absence of efficient chemotherapy, which is severely hampered by the blood-brain barrier. However, the leaky blood-brain-tumour barrier forms upon tumour growth and vascularization, allowing targeted nanocarrier-mediated drug delivery. The homotypic targeting ability of cell-membrane fragments obtained from cancer cells means that these fragments can be exploited to this aim. In this experimental work, injectable nanoemulsions, which have a long history of safe clinic usage, have been wrapped in glioma-cell membrane fragments via co-extrusion to give targeted, homogeneously sized, sterile formulations. These systems were then loaded with three different chemotherapeutics, in the form of hydrophobic ion pairs that can be released into the target site thanks to interactions with physiological components. The numerous assays performed in two-dimensional (2D) and three-dimensional (3D) cell models demonstrate that the proposed approach is a versatile drug-delivery platform with chemo-tactic properties towards glioma cells, with adhesive interactions between the target cell and the cell membrane fragments most likely being responsible for the effect. This approach's promising translational perspectives towards personalized nanomedicine mean that further in vivo studies are foreseen for the future.

Highly Efficient and Reproducible Sonochemical Synthesis of ZnO Nanocrystals.

Sonochemical synthesis can be a facile, fast, efficient, versatile and economical way to prepare a large variety of conventional or novel nanostructured materials (metallic, magnetic, semiconducting, polymeric, etc.). In this work, zinc oxide nanocrystals were synthesized by irradiating and heating at 90 °C in a commercial ultrasonic bath a water solution of zinc nitrate hexahydrate and ammonia solution or hexamethylenetetramine as base catalysts. The evolution of the powder morphology and its crystalline structure were investigated at different times of ultrasonic irradiation (0-9 hours) and compared with those of samples obtained by only heating the solutions in a muffle furnace in order to enlighten the growth mechanism. It resulted that: i) the crystal morphology depends on the selected base, ii) for samples obtained by using ultrasounds, the homogeneity of the powders depends on the irradiation time, iii) by comparing all samples obtained at 7 hours of heating, the aspect ratio of the crystals is higher for those that also underwent to ultrasounds.

Ultrasmall Solid-Lipid Nanoparticles via the Polysorbate Sorbitan Phase-Inversion Temperature Technique: A Promising Vehicle for Antioxidant Delivery into the Skin.

Solid lipid nanoparticles promote skin hydration via stratum corneum occlusion, which prevents water loss by evaporation, and via the reinforcement of the skin's lipid-film barrier, which occurs through the adhesion of the nanoparticles to the stratum corneum. The efficacy of both phenomena correlates with lower nanoparticle size and the increased skin permeation of loaded compounds. The so-called Polysorbate Sorbitan Phase-Inversion Temperature method has, therefore, been optimized in this experimental work, in order to engineer ultrasmall solid-lipid nanoparticles that were then loaded with α-tocopherol, as the anti-age ingredient for cosmetic application. Ultrasmall solid-lipid nanoparticles have been proven to be able to favor the skin absorption of loaded compounds via the aforementioned mechanisms.

Microwave-Assisted Reductive Amination of Aldehydes and Ketones Over Rhodium-Based Heterogeneous Catalysts.

Microwave (MW)-assisted reductive aminations of aldehydes and ketones were carried out in the presence of commercial and homemade heterogeneous Rh-based catalysts. Ultrasound (US) was used to improve dispersion and stability of metal nanoparticles, while commercial activated carbon and carbon nanofibers were used as supports. Moreover, various bio-derived molecules were selected as substrates, and aqueous ammonia was used as a cheap and non-toxic reagent. MW combined with heterogeneous Rh catalysts gave a 98.2 % yield in benzylamine at 80 °C with 10 bar H2 for 1 h; and a 43.3 % yield in phenylethylamine at 80 °C and 5 bar H2 for 2 h. Carbon nanofibers proved to be a better support for the metal active phase than simple activated carbon, since a limited yield in benzylamine (10.6 %) but a high selectivity for the reductive amination of ketones was obtained. Thus, raspberry ketone was converted to raspberry amine in a 63.0 % yield.

Interaction of Nanodiamonds with Water: Impact of Surface Chemistry on Hydrophilicity, Aggregation and Electrical Properties.

In recent decades, nanodiamonds (NDs) have earned increasing interest in a wide variety of research fields, thanks to their excellent mechanical, chemical, and optical properties, together with the possibility of easily tuning their surface chemistry for the desired purpose. According to the application context, it is essential to acquire an extensive understanding of their interaction with water in terms of hydrophilicity, environmental adsorption, stability in solution, and impact on electrical properties. In this paper, we report on a systematic study of the effects of reducing and oxidizing thermal processes on ND surface water adsorption. Both detonation and milled NDs were analyzed by combining different techniques. Temperature-dependent infrared spectroscopy was employed to study ND surface chemistry and water adsorption, while dynamic light scattering allowed the evaluation of their behavior in solution. The influence of water adsorption on their electrical properties was also investigated and correlated with structural and optical information obtained via Raman/photoluminescence spectroscopy. In general, higher oxygen-containing surfaces exhibited higher hydrophilicity, better stability in solution, and higher electrical conduction, although for the latter the surface graphitic contribution was also crucial. Our results provide in-depth information on the hydrophilicity of NDs in relation to their surface chemical and physical properties, by also evaluating the impacts on their aggregation and electrical conductance.

Methodology to define biological reference values in the environmental and occupational fields: the contribution of the Italian Society for Reference Values (SIVR).

BACKGROUND: Biological reference values (RVs) explore the relationships between humans and their environment and habits. RVs are fundamental in the environmental field for assessing illnesses possibly associated with environmental pollution, and also in the occupational field, especially in the absence of established biological or environmental limits. OBJECTIVES: The Italian Society for Reference Values (SIVR) determined to test criteria and procedures for the definition of RVs to be used in the environmental and occupational fields. METHODS: The paper describes the SIVR methodology for defining RVs of xenobiotics and their metabolites. Aspects regarding the choice of population sample, the quality of analytical data, statistical analysis and control of variability factors are considered. The simultaneous interlaboratory circuits involved can be expected to increasingly improve the quality of the analytical data. RESULTS: Examples of RVs produced by SIVR are presented. In particular, levels of chromium, mercury, ethylenethiourea, 3,5,6-trichloro-2-pyridinol, 2,5-hexanedione, 1-hydroxypyrene and t,t-muconic acid measured in urine and expressed in micrograms/g creatinine (µg/g creat) or micrograms/L (µg/L) are reported. CONCLUSIONS: With the proposed procedure, SIVR intends to make its activities known to the scientific community in order to increase the number of laboratories involved in the definition of RVs for the Italian population. More research is needed to obtain further RVs in different biological matrices, such as hair, nails and exhaled breath. It is also necessary to update and improve the present reference values and broaden the portfolio of chemicals for which RVs are available. In the near future, SIVR intends to expand its scientific activity by using a multivariate approach for xenobiotics that may have a common origin, and to define RVs separately for children who may be exposed more than adults and be more vulnerable.

Antibiotic-loaded acrylic bone cements: an in vitro study on the release mechanism and its efficacy.

An in vitro study was carried out in order to investigate the antibiotic release mechanism and the antibacterial properties of commercially (Palacos® R+G and Palacos® LV+G) and manually (Palacos® R+GM and Palacos® LV+GM) blended gentamicin-loaded bone cements. Samples were characterized by means of scanning electron microscopy (SEM) and compression strength was evaluated. The antibiotic release was investigated by dipping sample in simulated body fluid (SBF) and periodically analyzing the solution by means of high pressure liquid chromatography (HPLC). Different antibacterial tests were performed to investigate the possible influence of blending technique on antibacterial properties. Only some differences were observed between gentamicin manually added and commercial ones, in the release curves, while the antibacterial effect and the mechanical properties seem to not feel the blending technique.

Application of the novel 5-chloro-2,2,3,3,4,4,5,5-octafluoro-1-pentyl chloroformate derivatizing agent for the direct determination of highly polar water disinfection byproducts.

A novel derivatizing agent, 5-chloro-2,2,3,3,4,4,5,5-octafluoropentyl chloroformate (ClOFPCF), was synthesized and tested as a reagent for direct water derivatization of highly polar and hydrophilic analytes. Its analytical performance satisfactorily compared to a perfluorinated chloroformate previously described, namely 2,2,3,3,4,4,5,5-octafluoropentyl chloroformate (OFPCF). The chemical properties (reactivity, selectivity, derivatization products, and their chromatographic and spectral features) for ClOFPCF were investigated using a set of 39 highly polar standard analytes, including, among others, hydroxylamine, malic and succinic acids, resorcinol, hydroxybenzaldehyde, and dihydroxybenzoic acid. Upon derivatization, the analytes were extracted from the aqueous solvent and analyzed by gas chromatography (GC)-mass spectrometry (MS) in the electron-capture negative ionization (ECNI) mode. Positive chemical ionization (PCI)-MS was used for confirming the molecular ions, which were virtually absent in the ECNI mass spectra. ClOFPCF showed good reaction efficiency, good chromatographic and spectroscopic properties (better than with OFPCF), good linearity in calibration curves, and low detection limits (0.3-1 microg/L). A unique feature of the derivatizations with ClOFPCF, and, in general, highly fluorinated chloroformates, is their effectiveness in reacting with carboxylic, hydroxylic, and aminic groups at once, forming multiply-substituted non-polar derivatives that can be easily extracted from the aqueous phase and determined by GC-ECNI-MS. The entire procedure from raw aqueous sample to ready-to-inject hexane solution of the derivatives requires less than 10 min. Another benefit of this procedure is that it produced stable derivatives, with optimal volatility for GC separation, and high electron affinity, which allows their detection as negative ions at trace level. In addition, their mass spectra exhibits chlorine isotopic patterns that clearly indicate how many polar hydrogens of the analyte undergo derivatization. Finally, derivatization with ClOFPCF was used successfully to identify 13 unknown highly polar disinfection byproducts (DBPs) in ozonated fulvic and humic acid aqueous solutions and in real ozonated drinking water.

Comparison of highly-fluorinated chloroformates as direct aqueous sample derivatizing agents for hydrophilic analytes and drinking-water disinfection by-products.

Four highly-fluorinated alkyl and aryl chloroformates, including 2,2,3,3,4,4,5,5-octafluoro-1-pentyl chloroformate (OFPCF), 2,3,4,5,6-pentafluorobenzyl chloroformate (PFBCF), 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octyl chloroformate (TDFOCF), and 2-(2,3,4,5,6-pentafluorophenoxy)-ethyl chloroformate (PFPECF), were synthesized and tested as reagents for the direct water derivatization of polar and hydrophilic analytes. The goal of this research was to develop an optimal derivatizing agent to aid in the identification of highly polar ozonation drinking water disinfection by-products (DBPs) that are believed to be missed with current analytical procedures. The chemical properties (reactivity, selectivity, derivatization products, and their chromatographic and spectral features) for the four chloroformates were investigated using a set of highly polar standard analytes, including malic and tartaric acids, hydroxylamine, valine, 2-aminoethanol, resorcinol, 1,3,5-trihydroxybenzene, and 2,4-dihydroxybenzoic acid. Upon derivatization, the analytes were extracted from the aqueous solvent and analyzed by gas chromatography (GC)-mass spectrometry (MS) in the electron capture negative ionization (ECNI) mode. Positive chemical ionization (PCI)-MS was used for confirmation of molecular ions that were weak or absent in ECNI mass spectra. Of the four derivatizing reagents tested, OFPCF showed the best performance, with good reaction efficiency, good chromatographic and spectroscopic properties, low detection limits (10-100 fmol), and a linear response more than two orders of magnitude. Further, the entire procedure from raw aqueous sample to ready-to-inject hexane solutions of the derivatives requires less than 10 min. PFBCF showed ideal applicability for derivatizing aminoalcohols and aminoacids. The two chloroformates with the highest intrinsic stability (TDFOCF and PFPECF) failed to derivatize some of the analytes. Finally, the OFPCF derivatizing agent was tested with simulated ozonated drinking water (aqueous fulvic acid treated with ozone), and three highly polar reaction by-products were determined.