Calorimetric Evaluation of Glycyrrhetic Acid (GA)- and Stearyl Glycyrrhetinate (SG)-Loaded Solid Lipid Nanoparticle Interactions with a Model Biomembrane

Glycyrrhetic acid (GA) and stearyl glycyrrhetinate (SG) are two interesting compounds from Glycyrrhiza glabra, showing numerous biological properties widely applied in the pharmaceutical and cosmetic fields. Despite these appreciable benefits, their potential therapeutic properties are strongly compromised due to unfavourable physical-chemical features. The strategy exploited in the present work was to develop solid lipid nanoparticles (SLNs) as carrier systems for GA and SG delivery. Both formulations loaded with GA and SG (GA-SLNs and SG-SLNs, respectively) were prepared by the high shear homogenization coupled to ultrasound (HSH-US) method, and we obtained good technological parameters. DSC was used to evaluate their thermotropic behaviour and ability to act as carriers for GA and SG. The study was conducted by means of a biomembrane model (multilamellar vesicles; MLVs) that simulated the interaction of the carriers with the cellular membrane. Unloaded and loaded SLNs were incubated with the biomembranes, and their interactions were evaluated over time through variations in their calorimetric curves. The results of these studies indicated that GA and SG interact differently with MLVs and SLNs; the interactions of SG-SLNs and GA-SLNs with the biomembrane model showed different variations of the MLVs calorimetric curve and suggest the potential use of SLNs as delivery systems for GA.     

Donkey Milk Fermentation by Lactococcus lactis subsp. cremoris and Lactobacillus rhamnosus Affects the Antiviral and Antibacterial Milk Properties

Background: Milk is considered an important source of bioactive peptides, which can be produced by endogenous or starter bacteria, such as lactic acid bacteria, that are considered effective and safe producers of food-grade bioactive peptides. Among the various types of milk, donkey milk has been gaining more and more attention for its nutraceutical properties. Methods: Lactobacillus rhamnosus 17D10 and Lactococcus lactis subsp. cremoris 40FEL3 were selected for their ability to produce peptides from donkey milk. The endogenous peptides and those obtained after bacterial fermentation were assayed for their antioxidant, antibacterial, and antiviral activities. The peptide mixtures were characterized by means of LC-MS/MS and then analyzed in silico using the Milk Bioactive Peptide DataBase. Results: The peptides produced by the two selected bacteria enhanced the antioxidant activity and reduced E. coli growth. Only the peptides produced by L. rhamnosus 17D10 were able to reduce S. aureus growth. All the peptide mixtures were able to inhibit the replication of HSV-1 by more than 50%. Seventeen peptides were found to have 60% sequence similarity with already known bioactive peptides. Conclusions: A lactic acid bacterium fermentation process is able to enhance the value of donkey milk through bioactivities that are important for human health.     

Molecular mechanism of drug photosensitization. Part 3. Photohemolysis sensitized by diflunisal.

The lysis of red blood cells photosensitized by diflunisal (DFN) was investigated. Photohemolysis is inhibited by butylated hydroxyanisole and reduced glutathione, but is unaffected by mannitol and enhanced by sodium azide; the presence of oxygen markedly reduces the lysis which is accelerated in anaerobic conditions. These results contrast with those expected for a photodynamic mechanism. High lytic activity is observed for pre-irradiated solutions, mainly under anaerobic conditions. Direct irradiation of DFN in buffer solution at pH 7.4 leads to the formation, under anaerobic conditions, of compound 2'-(2',4'-difluoro-3'-carboxy-[1',1'-biphenyl]-4'-oxy)-4'- fluoro-4-hydroxy-[1,1'-biphenyl]-3-carboxylic acid (PhP), whereas under aerobic conditions formation of PhP is accompanied by unidentified photo-oxidation products; only compound PhP displays strong lytic activity. The overall results for DFN-photosensitized hemolysis suggest a mechanism involving a concerted action of free radicals, superoxide anion, singlet oxygen and sensitizer photoproducts.     

Direct mass spectrometry of polymers. X. Primary thermal fragmentation processes in totally aromatic polyesters

The thermal decomposition of a series of isomeric poly-(oxphthaloyloxyphenylenes) (I–IV) and poly(m-hydroxybenzoic acid) (V) was studied by Direct Pyrolysis–Mass Spectrometry. The results indicate that intramolecular exchange reactions predominate in the primary thermal fragmentation processes, causing the formation of cyclic oligomers which are subsequently cleaved to open-chain fragments. The size and relative abundance of the cycles produced appear to be strongly influenced by steric factors, i.e., by the structure (para or meta) of the repeating unit in each polymer. Remarkably, in the case of poly(m-hydroxybenzoic acid) the formation of cyclic oligomers containing up to seven repeating units is observed.     

MOLECULAR MECHANISM OF DRUG PHOTOSENSITIZATION 7. PHOTOCLEAVAGE OF DNA SENSITIZED BY SUPROFEN

Abstract— Ultraviolet-A irradiation of a suprofen (2-[4-(2-thenoyl)phenyl]propionic acid) (SPF) buffered solution (pH 7.4) in the presence of supercoiled pBR322 DNA leads to single strand breaks with the formation of an open circular form and subsequent linearization of the plasmid. On the basis of agarose gel electrophoresis data of samples irradiated in an air-saturated solution or in an oxygen-modified atmosphere, and the effects of sodium azide, D₂O, mannitol, copper(II), superoxide dismutase, 2-H-propanol, deferoxamine and surfactants, we suggest a photosensitization mechanism involving singlet oxygen and free radicals. The higher rate of photocleavage in nitrogen compared to that in an air-saturated solution and the results obtained from oxygen consumption measurements support the hypothesis that both the type I and type II photosensitization mechanisms are operative and that oxygen quenches the excited state of the irradiated drug. The photosensitization model applied was in agreement with that previously applied to cell membrane SPF photoinduced damage. Interaction of the drug with DNA, studied through circular dichroism and fluorescence anisotropy, probably occurs through a surface binding mode. The experimental techniques used for assessing the photodamaging activity of this drug may be useful for screening of phototoxic compounds in the environment and for determining the active species involved.     

Effect of N-methyl substitution on the thermal decomposition processes in aliphatic–aromatic polyamides

The thermal decomposition processes of two polyamides, derived from succinic acid and two aromatic diamines, were studied by direct pyrolysis mass spectrometry. Fast atom bombardment (FAB) mass spectrometry has been also used in order to provide additional information for the elucidation of the thermal degradation mechanism of the polymers investigated. FAB mass spectra, obtained by introducing in the FAB ion source the solid residues from polymer pyrolysis performed in thermogravimetric experiments, allowed the detection of diagnostic compounds up to about 1600 amu. Our results indicate that the thermal stability of the N-methyl-substituted polyamide is higher than that of the unsubstituted polyamide. The difference in the thermal degradation mechanism accounts for the difference in the thermal stability of the two polyamides. In fact, the unsubstituted polyamide decomposes via an intramolecular exchange and a concomitant N? H hydrogen transfer process with formation of compounds with amine and/or succinimide end groups. Instead, the N-methyl-substituted polyamide decomposes via an α C? H hydrogen transfer process from the methyl group to the nitrogen atom with formation of compounds with amine and/or 2,5-piperidinedione end groups.     

Separation and quantitation of metal ions by 4-(2-pyridylazo)resorcinol complexation in capillary electrophoresis-electrospray ionisation mass spectrometry

The possibility of using capillary electrophoresis-electrospray ionisation (ESI)/MS to separate and quantify cobalt and iron was explored. It was necessary to tackle and overcome problems from different sources, some of them being rather unpredictable. The results obtained suggest the occurrence of oxidation processes of metal ions during the formation of the electrospray. The quantitative oxidation of cobalt(II) to cobalt(III), a process at our knowledge never described before, appears particularly interesting. The results obtained, though not optimised for sensitivity appear promising, since a limit of detection of the order of tenths of picograms was obtained. Further, from the comparison with the results obtained by optical detection, the use of CE-ESI/MS appears advantageous.     

Effect ofβ-cyclodextrin complexation on the photohaemolitic activity induced by Ketoprofen and Naproxen sensitization

Red blood cell lysis photosensitized by two non-steroidal anti-inflammatory drugs Naproxen (NAP) and Ketoprofen (KPF) was investigated in the presence of -cyclodextrin (-Cyd). The photohaemolysis was inhibited by the addition of -Cyd both for NAP and, to a lesser extent, for KPF. The protective action was found only in a restricted range of concentration of -Cyd. Higher amounts of -Cyd interfered with the resistance of the cell to the osmotic shock induced by the photosensitization process. The complexing action of -Cyd was ascertained through UV-vis absorption spectroscopy, induced circular dichroism and emission spectroscopy.The isolated complexes Naproxen--Cyd (NAP--Cyd) and Ketoprofen--Cyd (KPF--Cyd) were found to protect from the photosensitized membrane damage induced by the two drugs, even if it occurred only in a limited range of concentration. This suggests a valid tool in alleviating thein vitro phototoxic consequences caused by these compounds, even if care has to be taken in therapeutic administration due to the presence of the uncomplexed -Cyd.     

Gluconjugates of 8-hydroxyquinolines as potential anti-cancer prodrugs

8-Hydroxyquinolines are systems of great interest in the field of inorganic and bioinorganic chemistry. They are metal-binding compounds and are known to exhibit a variety of biological activities, such as antibacterial and anticancer activities. Among these systems, clioquinol has been the focus of a renewed interest in recent years. In this scenario, we synthesized and characterized the new clioquinol glucoconjugate, 5-chloro-7-iodo-8-quinolinyl-β-D-glucopyranoside in order to compare this system to that of clioquinol. We also synthesized, 8-quinolinyl-β-D-glucopyranoside, an 8-hydroxyquinoline glucoconjugate. The reason for the development of glucoconjugates is the glucose avidity, and the over-expression of glucose transporters in cancer cells. Here we demonstrate that glycoconjugates are cleaved in vitro by β-glucosidase and these systems exhibit antiproliferative activity against different tumor cell lines in the presence of copper(II) ions.     

Photoluminescence of a covalent assembled porphyrin-based monolayer: optical behavior in the presence of O2

The optical O(2) recognition capability of a covalently assembled monolayer (CAM) of 5,10,15-tri-{p-dodecanoxyphenyl}-20-(p-hydroxyphenyl) porphyrin on silica-based substrates was studied at room temperature by both UV-vis and photoluminescence (PL) measurements. The optical properties of this robust monolayer setup appear to be highly sensitive to the O(2) concentration in N(2). Both UV-vis and PL measurements were used to study the porphyrin-oxygen interactions. The monolayer-based sensor exhibits a short response time and can be restored within seconds. The oxygen-induced luminescence quenching of the monolayer involves both ground and excited states. The proposed mechanism responsible for the luminescence quenching involves different kinds of interactions between the monolayer and O(2).