Strategies to control the particle size distribution of poly-epsilon-caprolactone nanoparticles for pharmaceutical applications

In this work turbulent precipitation through solvent displacement for the production of poly-epsilon-caprolactone (PCL) nanoparticles is investigated; two different PCL molecular weights have been employed, using acetone and water as solvent and anti-solvent, respectively. The main important thermodynamic and kinetic parameters, such as solubility and interfacial tension of PCL in water-acetone mixtures, are determined and the effect of the process operating conditions on the final particle size distribution is also investigated. Particles produced under different conditions into a Confined Impinging Jets Reactor (CIJR) were characterized by Dynamic Light Scattering, Zeta potential measurements and Scanning Electronic Microscopy. Results clearly show the strong effect of mixing on the particle size distribution and how mixing must be controlled in order to obtain a product with particular characteristics. Eventually the measured thermodynamic and kinetic parameters are used to interpret the obtained experimental data.     

Fatty acid composition and volatile compounds of caviar from farmed white sturgeon (Acipenser transmontanus)

The present study was conducted to characterize caviar obtained from farmed white sturgeons (Acipenser transmontanus) subjected to different dietary treatments. Twenty caviar samples from fish fed two experimental diets containing different dietary lipid sources have been analysed for chemical composition, fatty acids and flavour volatile compounds. Fatty acid make up of caviar was only minimally influenced by dietary fatty acid composition. Irrespective of dietary treatments, palmitic acid (16:0) and oleic acid (OA, 18:1 n-9) were the most abundant fatty acid followed by docosahexaenoic acid (DHA, 22:6 n-3) and eicopentaenoic (EPA, 20:5 n-3). Thirty-three volatile compounds were isolated using simultaneous distillation-extraction (SDE) and identified by GC-MS. The largest group of volatiles were represented by aldehydes with 20 compounds, representing the 60% of the total volatiles. n-Alkanals, 2-alkenals and 2,4-alkadienals are largely the main responsible for a wide range of flavours in caviar from farmed white surgeon.     

Preclinical pharmacokinetics comparison between resveratrol 2-hydroxypropyl-β-cyclodextrin complex and resveratrol suspension after oral administration

Trans-Resveratrol (RV) is a natural polyphenol characterized by interesting pleiotropic potentials and health benefits, but its administration is hampered by a unsatisfactory pharmacokinetics. Various approaches have been identified to circumvent it: among them, 2-hydroxypropyl-β-cyclodextrins (HPβCD) are valuable strategy. Here, we compare the employment of HPβCD based formulation with a resveratrol nanosupension (obtained by diluting a RV ethanol solution with PBS, added of 0.05 % hydroxyethylcellulose) to improve RV bioavailability after oral administration to mice. The inclusion of RV in HPβCD was confirmed by differential scanning calorimetry, Fourier transformed infrared spectroscopy, and phase solubility study. The two formulations were orally administered to BALB-c mice. RV concentrations in plasma and tissues were detected at different time (0–120 min) by HPLC method. HPβCD complexation mediate a approximately fourfold increment in plasma RV C_max and  approximately twofold augment of RV AUC_0-120 in comparison with RV nanosuspension. Similar increased concentrations were observed in heart, liver, kidney and gut. In particular, HPβCD mediated a 5.5-folds increase of resveratrol concentration in the intestine, in comparison to the nanosuspension. In conclusion, based on our results, HPβCD complexation is a promising approach to increase the oral bioavailability of RV. Moreover, the achievement of high concentrations in gut suggested a potential employment of oral RV-HPβCD as anti-inflammatory/chemopreventive agent in this tissue.     

First principles studies on boron sites in zeolites

A systematic computational investigation on protonated and nonprotonated boron-containing zeolites (boralites), performed by using different periodic density functional theory approximations, is presented. Both minimum energy structures and finite temperature behavior of model boron sodalites were analyzed. All of the adopted computational schemes agree in predicting an acid site composed of a silanol Si-OH group loosely linked to a planar BO(3) structure in the protonated system and a BO(4) tetrahedral site in the sodium-containing zeolite. Calculated structural and vibrational properties are in line with experimental data. Comparisons of the protonated boralite site with Al and Ga zeolitic acid sites are discussed as well. Results indicate that this class of mild acid catalysts is characterized by significant framework flexibility and pronounced thermal effects due to the loosely bound acid site.     

Chromatographic and electrophoretic methods for the analysis of phenethylamine [corrected] alkaloids in Citrus aurantium

Citrus aurantium (bitter orange) is a plant belonging to the family Rutaceae, whose fruit extracts have been used recently for the treatment of obesity. The most important biologically active constituents of the C. aurantium fruits are phenethylamine alkaloids (i.e. octopamine, synephrine, tyramine, N-methyltyramine and hordenine). Synephrine is a primary synthesis compound with pharmacological activities such as vasoconstriction, elevation of blood pressure and relaxation of bronchial muscle. Synephrine is present in the peel and the edible part of Citrus fruit. Of the adrenergic amines of natural origin, synephrine has been found to be the main constituent of C. aurantium fruits and extracts; the other alkaloids are either absent or present in only low concentrations. It is known that synephrine and the other amines found in C. aurantium have adverse effects on the cardiovascular system, owing to adrenergic stimulation. In light of the great commercial proliferation of C. aurantium herbal medicines in recent years, this review provides an overview of various extraction, separation and detection techniques employed for the qualitative and quantitative determination of the alkaloids in C. aurantium and related species. The application of chromatographic and electrophoretic methods for the separation and determination of these active components in C. aurantium plant material and derivatives are described. Since synephrine is a chiral compound, enantioselective chromatographic and electrophoretic techniques for the analysis of synephrine enantiomers in natural products are presented. Furthermore, examples of identification of these active compounds in complex matrices by hyphenated methods, such as gas chromatography-mass spectrometry and high-performance liquid chromatography-mass spectrometry, are described. The advantages and limitations of these separation and identification methods are assessed and discussed.     

FT-IR study of the nature and stability of NOx surface species on ZrO2, VOx/ZrO2 and MoOx/ZrO2 catalysts

The adsorption of NO, NO/O₂ mixtures and NO₂ on pure ZrO₂ and on two series of catalysts supported on ZrO₂, one containing vanadia and the other molybdena (ZV and ZMo, respectively), has been investigated. The V and Mo surface contents of the latter were ≤3 atoms nm⁻² and ≤5 atoms nm⁻², respectively. All samples had been previously submitted to a standard oxidation treatment. On all samples, only extremely minor amounts of NO_x surface species are formed by NO interaction at room temperature (RT). NO_x surface species are formed in greater amounts on pure ZrO₂ when NO and O₂ are coadsorbed at RT; they are mainly nitrites, small amounts of nitrates, and small amounts of (O₂NO−H)^δ− species; when ZrO₂ is warmed to 623 K in the NO/O₂ mixture, nitrites decrease, nitrates and (O₂NO−H)^δ− species increase. The same NO_x species as on the ZrO₂ surface free from V (or Mo) are formed on ZV (or ZMo) samples with surface V (or Mo) density <1.5 atoms nm⁻²; however, they occur in decreased amount with increasing V (or Mo) coverage. On ZV samples with a surface V density of 1.5–3 atoms nm⁻² (or ZMo samples with a surface Mo density of 1.5–5 atoms nm⁻²) when NO and O₂ are coadsorbed at RT, there is formation of small amounts of nitrites, nitrates (both on ZrO₂ surface free from V (or Mo) and at the edges of V- or Mo-polyoxoanions) and NO₂ ^δ+ species, associated with V⁵⁺ (or Mo⁶⁺) of very strong Lewis acidity; when samples are warmed up 623 K in the NO/O₂ mixture, nitrites disappear, nitrates increase, NO₂ ^δ+ species remain constant or slightly decrease. When NO₂ is allowed into contact at RT with oxidized samples, surface situations almost identical to those obtained for each sample warmed to 623 K in NO/O₂ mixture is reached. The NO_x surface species stable at 623 K, the temperature at which catalysts show the best performance in the selective catalytic reduction (SCR) of NO by NH₃, are nitrates, both on ZrO₂ and on polyvanadates or polymolybdates at high nuclearity. On the contrary, nitrites and NO₂ ^δ+ species are unstable at 623 K.     

Polyurethane Based Materials for the Production of Biomedical Materials

Polyurethanes (PUs) composed by hard and soft segments have been extensively used in the manufacturing of biocompatible prosthesis and medical devices. A broad variety of PUs can be obtained by modifying the balance between both segments. In the present work, different basically-flexible PUs have been prepared by employing different combinations of aliphatic hexamethylene diisocyanate, poly(ethylene glycol) (Mw 400 Da), poly(ϵ-caprolactone) diol (Mw 530 Da), and 1,4-butanediol. Thermal analysis of the synthesized PUs demonstrated high thermal stability and the assumption of glassy state well below room temperature, in agreement with their marked flexibility. Morphological characterization of PUs films indicated that films prepared by spin coating were smoother and more homogeneous than those obtained by casting. Biological assays performed by using 3T3/BALB-C mouse embryo fibroblast cell line confirmed the absence of toxicity and hence the biocompatibility of PU-films.     

A New Kid on the Block: Sacituzumab Govitecan for the Treatment of Breast Cancer and Other Solid Tumors

Human trophoblast cell-surface antigen-2 (Trop-2) is a membrane glycoprotein involved in cell proliferation and motility, frequently overexpressed in epithelial tumors. Thus, it represents an attractive target for anticancer therapies. Sacituzumab govitecan (SG) is a third-generation antibody-drug conjugate, consisting of an anti-Trop-2 monoclonal antibody (hRS7), a hydrolyzable linker, and a cytotoxin (SN38), which inhibits topoisomerase 1. Specific pharmacological features, such as the high antibody to payload ratio, the ultra-toxic nature of SN38, and the capacity to kill surrounding tumor cells (the bystander effect), make SG a very promising drug for cancer treatment. Indeed, unprecedented results have been observed with SG in patients with heavily pretreated advanced triple-negative breast cancer and urothelial carcinomas, and the drug has already received approval for these indications. These results are coupled with a manageable toxicity profile, with neutropenia and diarrhea as the most frequent adverse events, mainly of grades 1–2. While several trials are exploring SG activity in different tumor types and settings, potential biomarkers of response are under investigation. Among these, Trop-2 overexpression and the presence of BRCA1/2 mutations seem to be the most promising. We review the available literature concerning SG, with a focus on its toxicity spectrum and possible biomarkers of its response.