Search

An absorption and circular dichroism spectroscopies investigation was carried out on the heteroaggregates formed in water upon the interaction of Chicago Sky Blue with four different cationic surfactants derived from ephedrine and pseudoephedrine and featuring hydrophobic tails of different length. The chirooptical features of the heteroaggregates indicate that hydrophobic interactions control the transcription of the chiral information from the surfactant to the supramolecular architectures they form with the dye. In fact, surfactants characterised by the same stereochemistry and by different length of the hydrophobic tails mediate the selection of the enantiomers of the same chiral topological arrangement. [ABSTRACT FROM AUTHOR]

Abstract: The uptake of two photosensitising agents (hematoporphyrin and chlorophyll a) by a highly pathogenic bacterium, namely methicillin-resistant Staphylococcus aureus (MRSA), has been studied by using unilamellar liposomes of different size, fluidity and electric charge as carriers. Optimal results are obtained by using hematoporphyrin embedded in fluid cationic vesicles composed by the monocationic lipid N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP), which yield an endocellular concentration of photosensitiser much higher than that obtained by incubation of the cells with the free porphyrin, yet promote a tighter binding and a more efficient photoinactivation of MRSA. Apparently, the photosensitiser is successfully transferred from the liposome to the bacterial cells when the presence of the tetrapyrrolic derivative does not appreciably perturb the native three-dimensional organisation of the lipid vesicle, such as it occurs with hematoporphyrin. On the other hand, chlorophyll, which causes a marked structural alteration of the DOTAP vesicles as shown by electron microscopy and fluorescence anisotropy measurements, does not show any detectable photocytotoxicity toward MRSA, contrary to what observed for the free dye. [Copyright &y& Elsevier]

A biomimetic system of cytochrome P450, constituted by [5-(4-(1-methylpyridinium))-10,15,20-triphenylporphyrinato] manganese(III) dichloride (Mn1) included in cetylpyridinium chloride (CPyCl) micellar phase, features good catalytic activity in the NaClO promoted epoxidation of styrene.A closely related system, i.e. [5-(4-(3-trimethylammonium) propyloxyphenyl)-10,15,20-tryphenyl-porphyrinato] manganese(III) dichloride (Mn2) in cetyltrimethylammonium bromide (CTAB), presents a lower reactivity, similar to that achieved in ethanol–water solvent mixture. A crossover experiment, i.e. that carried out with Mn1/CTAB system, shows intermediate degree of conversion. These findings indicate that the catalytic properties of the investigated systems are deeply influenced by the specific non-covalent interactions established among the catalyst, substrate, and surfactant. [Copyright &y& Elsevier]

(+)‐Usnic acid (UA) is a natural substance that displays pharmacological activity, but it is barely soluble in water, so it was included in liposomes in order to study its properties. First, the effects of phospholipid structure and loading methodology on UA entrapment efficacy were evaluated. Then, the physicochemical and biological properties (UA delivery efficacy to Staphylococcus aureus bacterial cells) of different liposome formulations containing structurally related amphiphiles derived from L‐prolinol were fully investigated. Entrapment efficiency of UA with passive loading by incubation was 80–100 molar percentage, which is related to lipophilicity of the drug and to the packing and fluidity of the bilayer. Some of the investigated formulations show the potential of UA in delivery systems (minimum inhibitory concentration of liposomal UA: 8 μg/mL) and even subtle variations of the molecular structure of lipids can significantly affect the liposomes' physicochemical properties and efficiency of drug release. [ABSTRACT FROM AUTHOR]

• Olive leaves and orange peels extracts rich in polyphenols were prepared by ultrasound assisted extraction. • Olive leaves and orange peels extracts were embedded in DOPC/Chol based liposomes prepared by sonication protocol. • Ultrasounds provided liposomes with suitable physicochemical features, good entrapment efficiency and storage stability. • The inclusion of olive leaves extract in sonicated DOPC/Chol liposomes enhanced its antimicrobial activity. Every year million tons of by-products and waste from olive and orange processing are produced by agri-food industries, thus triggering environmental and economic problems worldwide. From the perspective of a circular economy model, olive leaves and orange peels can be valorized in valuable products due to the presence of bioactive compounds such as polyphenols exhibiting beneficial effects on human health. The aqueous extracts of olive leaves and orange peels rich in phenolic compounds were prepared by ultrasound-assisted extraction. Both extracts were characterized in terms of yield of extraction, total phenolic content and antioxidant capacity; the polyphenolic profiles were deeper investigated by HPLC-MS analysis. Each extract was included in liposomes composed by a natural phospholipid, 1,2-dioleoyl- sn -glycero-3-phosphocholine, and cholesterol prepared according to the thin-layer evaporation method coupled with a sonication process. The antimicrobial activity of the extracts, free and loaded in liposomes, was investigated according to the broth macrodilution method against different strains of potential bacterial pathogenic species: Staphylococcus aureus (NCIMB 9518), Bacillus subtilis (ATCC 6051) and Enterococcus faecalis (NCIMB 775) as Gram -positive, while Escherichia coli (NCIMB 13302), Pseudomonas aeruginosa (NCIMB 9904) and Klebsiella oxytoca (NCIMB 12259) as Gram -negative. The encapsulation of olive leaves extract in liposomes enhanced its antibacterial activity against S. aureus by an order of magnitude. [ABSTRACT FROM AUTHOR]

• The activity of liposomal usnic acid was investigated on S. epidermidis biofilm. • Structurally related surfactants were used for liposomes preparation. • The separated effect of glucosylation and of positive charge was evaluated. • UA included in glucosylated cationic liposomes is still active at MIC/5. Because of the increased incidence of infections caused by resistant pathogens, due to the intensive use of antibiotics, there is an urgent need to develop new therapeutic strategies against bacteria, possibly based on non conventional drugs. (+)-Usnic acid is a natural compound that exerts a potent antibacterial activity, however its clinical application is hampered by its scarce solubility in water. Usnic acid was included, by both passive and active loading techniques, in liposomes containing structurally related glucosylated amphiphiles. Liposome formulations were characterized from the physicochemical point of view and their activity against biofilm associated Staphylococcus epidermidis was also evaluated. The inclusion of usnic acid in glucosylated cationic liposomes promotes its penetration in biofilm matrix with a consequent increase of its antimicrobial activity. The effect of both cationic charge and sugar residue seems to be synergistic. [ABSTRACT FROM AUTHOR]

Liposomes functionalized on their surface with carbohydrates (glycoliposomes) represent an optimal approach for targeting of drugs to diseased tissues in vivo , thanks to biocompatibility, low toxicity and easy manufacturing of these lipid nanoparticles. Here we report on the study of liposomes including a novel glycosylated amphiphile and on the comparison of their features with those of glycosylated analogues described previously. Further, the capability of the different glucosylated formulations to interact with three breast cancer cell lines was investigated. Our results show that the hydrophobic portion of the lipid bilayer strongly influences both the properties and the internalization of glycosylated liposomes. Unlabelled Image • Liposomes containing conventional and twin glucosylated surfactants were studied. • Also the length of the hydrophilic spacer of the glucosylated surfactants differ. • The interaction of liposomes with three breast cancer cell lines was investigated. • The hydrophobic portion of the bilayer is crucial for liposomes internalization. [ABSTRACT FROM AUTHOR]

Hypothesis Bolaamphiphiles are characterized by wide polymorphism of their aggregates, due to the connection of the headgroups that renders their investigation very intriguing in several technological applications. Some bolaamphiphiles displaying the triphenylphosphonium motif (TPP-bolaamphiphiles) were previously explored for their ability in crossing the mitochondrial membranes but their colloidal features, which are crucial for the potential development of an effective drug delivery system, were never investigated. Experiments Single chain TPP-bolaamphiphiles, featuring chains of 12, 16, 20 and 30 methylene units, were synthesized and their aggregation features (Krafft point , cac , dimensions, morphology, stability) were investigated by conductivity, dialysis, transmission electron microscopy, Raman spectroscopy, dynamic and dielectrophoretic laser light scattering measurements. Findings All the TPP-bolaamphiphiles spontaneously self-assemble into vesicles, independently of the chain length. The bolaamphipile with the longest chain forms monodispersed vesicles whereas for the other bolaamphiphiles two distinct populations of vesicles are observed. All vesicles are not equilibrium systems, in particular vesicles formed by the bolaamphiphiles featuring 20 and 30 methylene units result notably stable to dilution thanks to both the tightening of molecular packing at increasing chain length and the progressive reduction of the monomer percentage in U-shaped conformation. These features make these TPP-bolaamphiphiles very attractive as minor components for the development of novel mitochondriotropic liposomes. [ABSTRACT FROM AUTHOR]

Phase properties and lateral distribution of components in lipid membranes are frequently investigated by fluorescence of pyrene-labeled lipids. In particular conditions, at specific component molar fractions, lipid bilayers can present regions organized in regular arrangements, hexagonal lattices, where the acyl chain form regular patterns around the pyrene tagged chain of the labeled component. Liposomes composed of a pyrenyl twin type amphiphile ( 1 ) bearing a pyrrolidinium headgroup and either 1,2-dimyristoyl- sn -glycero-phosphocholine or 1,2-dioleoyl- sn -glycero-phosphocholine were investigated by fluorescence spectroscopy and Langmuir compression isotherm techniques in a restricted range of molar fraction, X 1 , (0.005-0.15) to evaluate the influence of composition, temperature and curvature radius on lipid organization and to assess the eventual organization in super lattice arrangements. Amphiphile 1 presents different characteristics with respect to the Pyr-PC usually used in similar investigations, both in terms of charge and conformational freedom, and its presence has a significant effect on membrane organization. Our results put in evidence that both temperature and the presence of unsaturation strongly influence the presence of hexagonal lattice in lipid bilayers. [ABSTRACT FROM AUTHOR]

The presence of carbohydrate-binding proteins ( i.e. lectins) on the surface of various bacterial strains and their overexpression in some tumor tissues makes the use of glycosylated liposomes a promising approach for the specific drug delivery in antibacterial and anti-cancer therapies. However, the functionalization of liposome surface with sugar moieties by glycosylated amphiphiles does not ensure the binding of sugar-coated vesicles with lectins. In fact, the composition and properties of lipid bilayer play a pivotal role in the exposure of sugar residues and in the interaction with lectins. The influence of the length of the hydrophilic spacer that links the sugar to liposome surface and of the presence of saturated or unsaturated phospholipids in the lipid bilayer on the ability of glucosylated liposomes to interact with a model lectin, Concanavalin A, was investigated. Our results demonstrate that both the chain length and the prensece of unsaturation, parameters that strongly affect the fluidity of the lipid bilayer, affect agglutination. In particular, agglutination is favored when liposomes are in the gel phase within a defined range of temperature. Moreover, the obtained results confirm that the length of the PEG spacer, that influences both lipid organization and the exposure of sugar moieties to the bulk, plays a crucial role in liposome/lectin interaction [ABSTRACT FROM AUTHOR]

Identification and quantification of bacteria affecting human life, directly causing diseases and indirectly contaminating natural ecosystems, are mostly carried out by expensive and time-consuming methods. There is the need for rapid and economic ways for detecting bacteria in the environment and in clinics. We propose the use of engineered liposomes for detecting bacteria in drinking water. Our approach exploits cationic liposomes functionalized with a surface potential-sensitive fluorophore, 4-heptadecylumbelliferone (C17-HC). The interaction between liposomes and bacteria involves a change in the surface potential experienced by C17-HC and switches on an optical signal. We investigated, by DLS, zeta-potential and fluorescence experiments, a large number of cationic liposomes formulated with a natural phospholipid 1,2-dipalmitoyl- sn -glycero-3-phosphocholine (DPPC) or 1,2-dioleoyl- sn -glycero-3-phosphocholine (DOPC), C17-HC, and one of three synthetic cationic components, differing from each other for the number of unsaturations on the polar ammonium head, two of which ad hoc synthesized. Then we evaluated the ability of liposomes to produce a fluorescent signal upon interaction with three bacterial strains, Staphylococcus aureus , Escherichia coli and Enterococcus faecalis ; moreover, we analyzed the fluorescent response of each liposome formulation in the presence of the three bacterial strains at the same time, in order to simulate a real scenario. We found that interaction with bacteria triggers an optical signal in six of the evaluated formulations, resulting responsive down to 10 2 CFU/mL of bacteria suspended in pipeline water coming from the water main of Rome (Italy). [ABSTRACT FROM AUTHOR]

5-Fluorouracil (5-FU) is a chemotherapic drug widely employed to treat a wide range of solid tumors. Unfortunately, it has a narrow therapeutic window and the level of its target enzymes in biological fluids of patients can vary considerably. On these premises, a new fluorescent lipid based sensor for the detection of thymidine phosphorylase, one of the target enzymes of 5-FU, was developed, to optimize patient treatment. Both cationic and anionic fluorescent liposomes containing both an amphiphile tail-tagged with a pyrene residue and a 5‐FU derivative were investigated. The effect of the presence of a bulky quencher (the bromine atom) covalently linked to the end of the alkyl chain of the anionic component on the emission signal was also evaluated. The interaction of liposomes with the target enzyme induces the occurrence of a fluorescent signal, at an extent that depends on the formulation, due to the variation of the excimer/monomer ratio. In particular, a promising specific result was obtained upon the interaction of the target enzyme with liposomes formulated with DOPC, the cationic fluorescent surfactant, the 5-FU derivative and 11-bromoundecaonic acid at 5/1/1/3 molar ratio. Langmuir compression isotherms allowed clarifying the influence of lipid organization on the response of the sensor. [ABSTRACT FROM AUTHOR]

Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with paradoxical reduced T cell activation, may represent a valid therapeutic target. We aimed to develop novel wild type PTPN22 short interfering RNA duplexes (siRNA) and optimize their delivery into Jurkat T cells and PBMC by using liposomal carriers. Conformational stability, size and polydispersion of siRNA in lipoplexes was measured by CD spectroscopy and DLS. Lipoplexes internalization and toxicity evaluation was assessed by confocal microscopy and flow cytometry analysis. Their effect on Lyp expression was evaluated by means of Western Blot and confocal microscopy. Functional assays through engagement of TCR signaling were established to evaluate biological consequences of down-modulation. Both Jurkat T cells and PBMC were efficiently transfected by stable custom lipoplexes. Jurkat T cell morphology and proliferation was not affected. Lipoplexes incorporation was visualized in CD3+ but also in CD3- peripheral blood immunotypes without signs of toxicity, damage or apoptosis. Efficacy in affecting Lyp protein expression was demonstrated in both transfected Jurkat T cells and PBMC. Moreover, impairment of Lyp inhibitory activity was revealed by increase of IL-2 secretion in culture supernatants of PBMC following anti-CD3/CD28 T cell receptor-driven stimulation. The results of our study open the pathway to future trials for the treatment of autoimmune diseases based on the selective inhibition of variant PTPN22 allele using lipoplexes of siRNA antisense oligomers. [ABSTRACT FROM AUTHOR]

The aggregation properties of a new cationic fluorescent amphiphile tagged on the hydrophobic tail with a pyrene moiety and bearing two hydroxyethyl functionalities on the polar headgroup were investigated by fluorescence experiments as pure components or in mixed liposomes containing an unsaturated phospholipid, 1,2‐dioleoyl- sn -glycero-3-phosphocholine, at different molar ratios. The obtained results put in evidence that the conformation and the miscibility of the lipids in the aggregates strongly influence the excimer/monomer ratio. Mixed monolayers at the same composition were investigated by Langmuir compression isotherms to deepen the understanding of lipid organization and miscibility, both in the polar and in the hydrophobic regions. The presence of two hydroxyethyl functionalities on the polar headgroup of the newly synthesized amphiphile exerts a shielding effect of the charge of the amphiphile increasing the compressibility of lipid components in contrast with the disturbing effect of the unsaturated acyl chains of the phospholipid. [ABSTRACT FROM AUTHOR]

The inclusion of pH-sensitive components in liposome formulations can allow a more controlled and efficient release in response to low pH typical of some pathological tissues and/or subcellular compartments. On the other hand decorating the surface of liposomes with sugar moieties attributes to lipid vesicles specificity toward lectins, sugar-binding proteins overexpressed in many tumor tissues. A novel multifunctional pH-sensitive glucosylated amphiphile was synthesized and characterized as pure aggregate component and in mixtures with a natural phospholipid. The comparison of the properties of the new glucosylated amphiphile with respect to those of a previously described cationic structural analogue demonstrates that the pH-sensitivity can strongly affect drug release, lipid organization, as well as the exposure of the glucose residues on liposome surface and their ability to interact with Concanavalin A, a plant lectin used as model system. [ABSTRACT FROM AUTHOR]

Over the past few years, chiral supramolecular assemblies have been successfully used for recognition, sensing and enantioselective transformations. Several approaches are available to control chirality of discrete assemblies (e.g., cages and capsules), but few are efficient in assuring chirality for micellar aggregates. Optically active amino acid-derived surfactants are commonly used to generate chiral spherical micelles. To circumvent this limitation, we benefited from the uniaxial growth of spherical micelles into long cylindrical micelles usually called wormlike or giant micelles, upon the addition of cosolutes. This paper describes the unprecedented formation of chiral giant micelles in aqueous solutions of cetyltrimethylammonium bromide (CTAB) upon increasing addition of enantiopure sodium salt of 1,1′-bi-2-naphthol (Na-binaphtholate) as a cosolute. Depending on the concentrations of CTAB and Na-binaphtholate, chiral gel-like systems are obtained. The transition from spherical to giant micellar structures was probed using rheology, cryo-transmission electron microscopy, polarimetry, and electronic circular dichroism (CD). CD can be effectively used to monitor the incorporation of Na-binaphtholate into the micelle palisade as well as to determine its transition to giant micellar structures. Our approach expands the scope for chirality induction in micellar aggregates bringing the possibility to generate "smart" chiral systems and an alternative asymmetric chiral environment to perform enantioselective transformations. [ABSTRACT FROM AUTHOR]

RATIONALE: Sulfur-vulcanized rubber is a three-dimensional polymer network, insoluble in all organic solvents. For this reason, vulcanization products are difficult to study and identify by conventional analytical techniques. To simplify this task, low molecular weight olefins have been used as model compounds (MCs) in place of rubber in vulcanization experiments. METHODS: In this work, the vulcanization process was investigated using squalene (SQ) as MC. By-products, intermediates and products were separated by semipreparative reversed-phase liquid chromatography (RPLC) with UV detection. Each fraction was collected, concentrated and characterized by flow injection analysis (FIA) and nonaqueous reversed-phase (NARP) LC coupled to positive atmospheric pressure chemical ionization mass spectrometry (APCI-MS). Under the latter conditions, an Information-Dependent Acquisition (IDA) was performed on a linear ion trap mass spectrometer to obtain structural information. RESULTS: Several vulcanized compounds containing up to three SQ molecules, cross-linked with chains involving up to 14 sulfur atoms overall, have been identified along with some of their oxidized products (epoxides and hydroperoxides). The FIA-MS spectra showed peak clusters, each of which included two-three subclusters; the interpretation was complicated by the occurrence of more ion species per product, by the unsaturation grade and by the characteristic isotopic distribution of sulfur. The enhanced product ion scan (EPI) spectra, acquired during the IDA experiments, supported the FIA-MS identification allowing one to count the number of sulfur atoms. CONCLUSIONS: The sensitivity of the developed analytical strategy was due to the enrichment factor achieved via semipreparative chromatography and the very good response of the APCI detection. Pattern fragmentation and chromatographic behavior simplified the identification of the cured compounds and their oxidized products, whose occurrence was related to the grade of oxidation of SQ used as reagent. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In a previous investigation, cationic liposomes formulated with new 5-FU derivatives, differing for the length of the polyoxyethylenic spacer that links the N 3 position of 5-FU to an alkyl chain of 12 carbon atoms, showed a higher cytotoxicity compared to free 5-FU, the cytotoxic effect being directly related to the length of the spacer. To better understand the correlation of the spacer length with toxicity, we carried out initial rate studies to determine inhibition, equilibrium and kinetic constants ( K I , K M , k cat ), and get inside inhibition activity of the 5-FU derivatives and their mechanism of action, a crucial information to design structural variations for improving the anticancer activity. The experimental investigation was supported by docking simulations based on the X-ray structure of thymidine phosphorylase (TP) from Escherichia coli complexed with 3′-azido-2′-fluoro-dideoxyuridin. Theoretical and experimental results showed that all the derivatives exert the same inhibition activity of 5-FU either as monomer and when embedded in lipid bilayer. [ABSTRACT FROM AUTHOR]

Pyrene lipids are useful tools to investigate membrane organization and intracellular lipid trafficking. The molecular interactions controlling the organization of lipid monolayers composed of a cationic amphiphile tagged with a pyrene residue and a saturated or unsaturated phospholipid, namely, 1,2-dimyristoyl-sn-glycero-3-phosphocholine and 1,2-dioleoyl-sn-glycero-3-phosphocholine, were investigated by Langmuir trough isotherms to understand how the molecular structure of the components and their relative amount affect the physicochemical properties of lipid monolayers. The obtained results show that the cationic headgroups and unsaturation of hydrophobic chains strongly affect the organization of the lipid monolayer as a function of the amount of components. On the other hand, the presence of the pyrene moiety does not seem to have a marked influence on the interaction within lipid assembly. [ABSTRACT FROM AUTHOR]

The functionalization of liposomes with glycosylated amphiphiles is an optimal strategy for targeted drug delivery, leading to enhanced efficacy as well as to reduced side effects of drugs. In fact, the presence of natural or synthetic glycolipids in vesicle formulations might increase their specificity toward lectins, a class of non-enzymatic sugar-binding proteins involved in cellular recognition and adhesion. The capability of a new glucosylated synthetic amphiphile to interact with Concanavalin A (Con A), a plant lectin used as model system, was investigated by a synergic experimental and computational approach, both as pure component and in formulation with a natural phospholipid. The comparison of the affinity with Con A of the new glucosylated amphiphile with respect to that of a previously described structural analogue demonstrates that the hydrophilic spacer length controls the exposure of the glucose residue on liposome surface, and consequently the recognition by the lectin. [ABSTRACT FROM AUTHOR]

Thespecificity of carbohydrate–lectin interaction has beenreported as an attractive strategy for drug delivery in cancer therapybecause of the high levels of lectins in several human malignancies.A novel cationic glucosylated amphiphile was therefore synthesized,as a model system, to attribute specificity toward d-glucosereceptors to liposome formulations. Fluorescence experiments demonstratedthat the monomeric glucosylated amphiphile is capable of interactingwith fluorescently labeled concanavalin A, a d-glucose specificplant lectin. The interaction of concanavalin A with liposomes composedof a phospholipid and the glucosylated amphiphile was demonstratedby agglutination observed by optical density and dynamic laser lightscattering measurements, thus paving the way to the preparation ofother glycosilated amphiphiles differing for the length of polyoxyethylenicspacer, the sugar moieties, and/or the length of the hydrophobic chain. [ABSTRACT FROM AUTHOR]

Abstract: Three new pyrrolidinium based surfactants were synthesized and characterized as pure aggregate components and in mixtures with 1,2-dimyristoyl-sn-glycero-3-phosphocholine to understand how the molecular structure of the cationic amphiphile and its mole percentage might affect the physicochemical properties of the resulting aggregates. The thermotropic behavior of the mixed liposomes was investigated by differential scanning calorimetry on multilamellar vesicles, whereas their size and surface potential were investigated on large unilamellar vesicles by dynamic laser light scattering and fluorescence experiments, respectively. The presence of either methoxy or hydroxy groups in the positions 3 and 4 of the pyrrolidinium ring as well as the presence of a second alkyl chain on pyrrolidinium nitrogen, controls the aggregates features. [Copyright &y& Elsevier]

Abstract: The interaction of neutral and anionic phospholipid liposomes, used as cell models, with cationic liposomes formulated with 1,2-dimyristoyl-sn-glicero-3-phosphocholine and stereomeric cationic gemini surfactants was investigated by differential scanning calorimetry, fluorescence experiments and dynamic laser light scattering. This study was aimed at rationalizing the different biological features shown by liposomes based on different gemini stereoisomers observed in previous investigations. In fact, to correlate the observed biological activity of liposomes with the molecular structure of their components is critical for a rational and systematic approach to the design of new carriers for drug delivery. The obtained results show that the different stereochemistry of the gemini surfactant controls the interaction and the extent of fusion with different cell models. [Copyright &y& Elsevier]

Abstract: Cationic liposomes are studied mainly as nonviral nucleic acid delivery systems and to a lesser extent as carriers/adjuvants of vaccines and as low-molecular-weight drug carriers. It is well established that the performance and the biological activity of liposomes in general are strongly related to their physicochemical properties. We investigated the thermotropic behavior and the size distribution of mixed cationic liposomes formulated with different percentages of 1,2 dimyristoyl-sn-glycero-3-phosphatidylcholine and one of four cationic amphiphiles characterized by a pyrrolidinium headgroup with the aim of achieving a better understanding of how the molecular structure of the cationic amphiphile and its mole percentage affect the physicochemical properties of the liposomes. Multilamellar vesicles and large unilamellar vesicles were studied by differential scanning calorimetry and turbidity, respectively, to characterize the thermotropic behavior and lipid phase, whereas dynamic light scattering was used to determine size distribution. This study shows that subtle modifications in the cationic amphiphile’s molecular structure and in liposome composition may have dramatic effects on the organization of the liposome bilayer and hence on the morphological and physicochemical features of the liposomes, thus being highly relevant to the biological features investigated previously. [Copyright &y& Elsevier]

Abstract: The interaction of phosphatidylcholine liposomes used as cell models, with cationic liposomes formulated with 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine and amphiphiles based on a pyrrolidinium headgroup was investigated by differential scanning calorimetry and fluorescence resonance energy transfer experiments. The results obtained showed that subtle variations in the formulation can influence lipid interactions and were correlated to a previous biological evaluation. [ABSTRACT FROM AUTHOR]

Abstract: The aggregates of three new isomeric chiral bola-amphiphiles have been taken into consideration as models for investigating chiral recognition in biological membranes. The recognition capabilities of the aggregates were explored following (by CD and HPLC experiments) the shift in the equilibrium between the inter-converting enantiomers of a biphenylic derivative and bilirubin, used as markers of chirality. The chiral recognition experiments were performed under different pH and concentration conditions. The results were compared with those relative to the aggregates formed by an equimolar mixture of single head/single chain amphiphiles that mimic the structure of the bola surfactant devoid of a covalent link. [ABSTRACT FROM AUTHOR]

Abstract: The recognition of the enantiomeric couples of ditryptophan in Langmuir films of N-hexadecanoyl-l-proline was investigated by surface pressure–area (π–A) isotherm measurements and Brewster angle microscopy experiments. The π–A isotherms relative to the films including the enantiomeric dipeptides show small differences whereas an evident enantiodiscrimination is observed by Brewster angle microscopy images. [Copyright &y& Elsevier]

Abstract: Two new steroidal spiroannulated calix[4]pyrroles 5 and 10, derived from bile acids (lithocholate), were prepared by the acid catalyzed condensation of methyl-3,3-bis(pyrrol-2-yl)-5β-cholan-24-oate 3 with carbonyl compounds and with 2,2′-propane-2,2-diylbis(1H-pyrrole), respectively. The new compounds were fully characterized by physicochemical methods. [Copyright &y& Elsevier]

Abstract: The need to preserve cultural heritage on paper requires the setting up of methods and treatments that can be applied to original documents. The cellulose main degradation processes are hydrolysis and oxidation. Only the first one has been widely investigated. The Istituto Centrale per la Patologia del Libro (ICPL) focused its attention on oxidation phenomena and studied a particular class of reducing agents, namely the borane-amine complexes. During the investigation it was found that the borane tert-butylamine complex, besides being the most promising reducing agent, was also able to react with carboxylic functions. In the present study 1H and 13C NMR, Pulsed field gradient NMR spectroscopy as well as Raman spectroscopy were used as analytical tools to disclose the mechanism of the interaction between the borane tert-butylamine complex and the carboxylic functions. Given the complexity of the paper/environment interactions and the subsequent degradation phenomena, we worked on simplified models based on small carbohydrate molecules in order to reproduce the behavior of degraded paper after reductive restoration. Modified D-glucose and D-cellobiose were used in this first step in order to set up the analytical methods before approaching more complex systems such as microcrystalline cellulose and paper. Our results give the experimental evidence that borane tert-butylamine complex is also able to neutralize acidic functions. This finding has important perspectives in paper restoration. [Copyright &y& Elsevier]

Glucosylated liposomes composed of the natural saturated phospholipid 1,2-dipalmitoyl- sn -glycero-3-phosphocholine (DPPC), cholesterol (Chol) and a cationic amphiphile featuring a glucosyl moiety (GL4), have been developed for delivering the antimicrobial trans -Resveratrol (RSV) to S. epidermidis , characterized by carbohydrate-specific adhesins able to recognize glucose. The cationic derivative of cholesterol, DC-Chol, was also included in liposome formulations, alone or in combination with GL4 , in order to explore the role of both cationic charge and sugar moiety in the interaction of liposomes with bacterial cells. RSV was included inside glucosylated cationic liposomes by the thin film method, coupled with either extrusion or sonication; liposome mean diameter, polydispersity index, surface charge, RSV entrapment efficiency and concentration have been measured by DLS, electrophoretic mobility, and HPLC. The antimicrobial activity of RSV-loaded liposomes was evaluated by monitoring the bacterial growth curves of two cell lines of Staphylococcus epidermidis , a slime positive strain (i.e. a strain able to form a biofilm) and a slime negative one. Results point out that, when the glucosylamphiphile GL4 is included in the formulation, only the extrusion protocol allows obtaining monodisperse liposomes with high RSV entrapment efficiency. The mean diameters of empty and resveratrol-loaded liposomes are all around 120–140 nm and size distribution are narrow, except for samples including GL4 at 5 molar percentage. Here the higher polydispersity index may be the indication of the occurrence of a restructuring phenomenon. The microbiological tests put in evidence a different response of the two bacterial cell lines to liposome treatments, in fact, the slime negative bacterial cells, that are not able to produce the extracellular polymeric substances, are more susceptible to the cationic charge of the liposomes and to the detergent effect of GL4. The most interesting results concern DPPC/Chol/ GL4 liposomes on the slime positive strain: this formulation, non-toxic in itself, displays an enhanced antibacterial efficacy with respect to free RSV, killing bacteria even at concentration tenfold under the MIC. [Display omitted] • Resveratrol glucoliposomes to treat Staphylococcus epidermidis infections. • Glucosyl-amphiphile targets Staphylococcus epidermidis. • Cationic glucosyl-amphiphile enhances liposomes binding to Staphylococcus epidermidis. • Cationic glucosylated liposomes improve resveratrol efficacy against Staphylococcus epidermidis. • RSV-loaded in cationic glucosylated liposomes kills Staphylococcus epidermidis at concentration tenfold under the MIC. [ABSTRACT FROM AUTHOR]

Abstract: The influence of the hydrophobic chain length on the chiral recognition capabilities of sodium N-acylprolinate micellar aggregates, used as biomembrane models, was investigated by 1H NMR on the enantiomer couples of ditryptophan. The length of the hydrophobic portion of the surfactant is shown to influence the mode of enantiodiscrimination. Interestingly the hydrophobic chain length also affects the site of binding of heterochiral enantiomers as well as their conformation inside the aggregates. [Copyright &y& Elsevier]

Abstract: The chirality of micellar aggregates formed by surfactants derived from l-proline was investigated by using two chiral biphenylic derivatives as probes of chirality. The investigation carried out by 1H NMR, circular dichroism, and HPLC on chiral phase demonstrates that chiral recognition may occur in sites of the aggregates far from the head-group stereogenic centers and it is due to interaction with a whole region of the aggregate rather than with a single monomer in the aggregate. Subtle changes of the structure of the monomer influence the aggregation properties of the surfactants and its expression of chirality. [Copyright &y& Elsevier]

Abstract: Antimicrobial photodynamic therapy is emerging as a promising therapeutic modality for bacterial infections. Our studies aim at identifying strategies for optimizing the antibacterial activity of porphyrin-type photosensitisers. The photoinactivation properties of a novel, positively charged meso-substituted porphyrin, namely 5-[4-(1-dodecanoylpyridinium)]-10,15,20-triphenyl-porphyrin were tested against a typically antibiotic-resistant pathogen, such as methicillin-resistant Staphylococcus aureus. This porphyrin is characterized by an unusually large quantum yield (0.95) for the generation of the hyper-reactive oxygen species, singlet oxygen. In spite of this, it exhibits a relatively low photosensitising activity against bacteria when dissolved in a homogeneous aqueous solution or incorporated into neutral lipid vesicles. On the contrary, a dramatic potentiation of the photocydal effect takes place when polycationic agents such as liposomes of N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride are used as carriers. The cationic carrier primarily acts as a disorganizing agent for the native three-dimensional architecture of the bacterial wall, thereby enhancing its permeability to the photosensitiser. Consequently, the drug can deeply penetrate into the plasma membrane, and rapidly impair selected enzymic activities leading to cell death. Thus, the combination of positively charged drugs and cationic delivery systems appears to represent an innovative modality for achieving an efficient antimicrobial activity and opens new avenues for the development of this phototherapeutic application. [Copyright &y& Elsevier]

Abstract: Enantiodiscrimination of ditryptophan enantiomers (l-Trp-l-Trp and d-Trp-d-Trp, l-Trp-d-Trp and d-Trp-l-Trp) was observed in bio-membrane models, such as micellar aggregates of 1,2-diheptanoyl-sn-glycero-3-phospatidylcholine (DHPC) and multilamellar vesicles of either 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or 1,2-dimyristoyl-sn-glycero-3-phospatidylcholine (DMPC) by solution 1H NMR and HR-MAS 1H NMR, respectively. The attainment of resolved signals, allowed the first detection of enantiodiscrimination at a molecular level, and the identification of the site of chiral recognition and of the interactions and conformations of homo- and heterochiral dipeptides in large-sized aggregates formed by a common component of bio-membranes. [Copyright &y& Elsevier]

While much is known about the self-assembly of lipids on nanoscale, our understanding of their biologically relevant mesoscale organization remains incomplete. Here, we show for a cationic gemini lipid a sharp and reversible transition from small vesicles with an average diameter of approximately 40 nm to giant vesicles (GVs) with an average diameter of approximately 11 μm. This transition is dependent on proper [NaCl] and specific temperature. Below this transition and in the vicinity of the air/water interface, a series of mesoscale morphological transitions was observed, revealing complex structures resembling biological membranes. On the basis of microscopy experiments, a tentative [NaCl] versus temperature shape/size phase diagram was constructed. To explain this unprecedented transition, we propose a novel mechanism whereby a specific interaction of Cl-counterion with the cationic gemini surfactant initiates the formation of a commensurate solute counterion lattice with low spontaneous curvature. In keeping with the high bending rigidity of NaCl crystal, this tightly associated ionic lattice enslaves membrane curvature and the mesoscale 3-D organization of this lipid. [ABSTRACT FROM AUTHOR]

Abstract: The preparation and the aggregation properties of new diastereomeric cationic cinchona derivatized surfactants are described. The opposite configuration of a stereogenic center strongly influences the morphology, the colloidal features, and the chiral recognition capabilities of the diastereomeric aggregates that have been investigated by various physico-chemical tools. [Copyright &y& Elsevier]

Abstract: Investigations aimed at clarifying the nature of geometrical domains of amidic sodium N-dodecanoyl-l-prolinate are reported. NMR investigations on the association of aromatic solutes with the aggregates formed by the amidic surfactant in water show the selective binding of some solutes to the Z domains. Fluorescence quenching experiments allowed us to measure the aggregation number of the aggregates. SAXS experiments gave the average size and structural features of the aggregates. A NMR ROESY experiment evidenced the mosaic-like nature of the domains inside the same aggregate. [Copyright &y& Elsevier]

Chiral recognition of the enantiomeric couples of ditryptophan and diphenylalanine was observed by ¹H NMR spectroscopy in micelles formed by sodium N-dodecanoyl-L-prolinate. Ditryptophan showed a selective association with the Z domains of the amidic aggregates, whereas diphenylalanine did not show any selectivity in the association. Partition coefficients between water and aggregates were evaluated by diffusion NMR experiments. Intramolecular distances of ditryptophan isomers associated with chiral aggregates were obtained by ROESY experiments and were used as constraints in molecular mechanics calculations. From these calculations, information on the conformation of the peptides in the chiral aggregates was obtained. [ABSTRACT FROM AUTHOR]

One of the most prominent hallmarks of apoptotic cells is the altered characteristics of their plasma membrane, with its blebbing and exposure of the anionic phospholipid, phosphatidylserine (PS), in the outer leaflet of the lipid bilayer. The latter feature provides the basis of distinguishing apoptotic cells from most normal cells due to staining with fluorescently labeled annexin V, binding specifically to PS. In this article, we report on the binding to apoptotic leukemic T cells (Jurkat cell line, treated with different apoptotic inducers) of cationic liposomes (CLs) composed of the cationic gemini surfactant SS-1 ((2S,3S)-2,3-dimethoxy-1,4-bis(N-hexadecyl-N,N-dimethylammonium)butane dibromide), the fluorescent lipid analog DOPRho (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(lissamine rhodamine B sulfonyl)), and POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine). Control cells showed negligible and irregular binding patterns of CLs, whereas apoptotic cells revealed a strongly augmented staining of their plasma membrane. Morphological observations and comparison with standard procedures for detecting apoptotic cells further demonstrated the binding of CLs to be intense for cells undergoing apoptosis. In addition, some apoptotic cells with higher caspase-3 activity also revealed more pronounced staining by CLs. Our data suggest that the binding of CLs to apoptotic cells is mediated through an electrostatic interaction between the positively charged head group of SS-1 and the translocated anionic phospholipid PS in the plasma membrane. Because the fluorescent lipid tracer can be freely selected, this approach provides convenient and versatile means for the fluorescence detection of apoptotic cells. [Copyright &y& Elsevier]

The inclusion behaviour of porphyrin derivative manganese [5-(4-(carboxyphenyl-(N-l-proline)))-10-15-20-triphenylporphyrinyl] chloride 1MnCl in micellar aggregates of sodium N-dodecanoyl-l-prolinate L-SDP and of sodium dodecylsulfate SDS has been studied by means of several spectroscopic techniques. The catalytic activity in the epoxidation reaction of some test chiral olefins has been also investigated. Comparison with the case of the related manganese[5-(4-carboxyphenyl)-10-15-20-triphenylporphyrinyl] chloride 2MnCl, gave evidence that suggests the presence of a chiral functionality on the periphery of porphyrin macrocycles affects their aggregation mode within the biomembrane models. This results in the modulation of their stereoselective Cytochrome P450 biomimetic activity. [Copyright &y& Elsevier]

Chiral discrimination of racemic 2,2′-diamino-6-(octanoyloxymethyl)biphenyl and 2,3′-diamino-6-(octanoyloxymethyl)biphenyl in micelles formed either by N-alkyl-N,N-dimethyl-N-(S)-(1-phenyl)ethylammonium bromide or sodium N-dodecanoyl-l-prolinate has been investigated by 1H NMR spectroscopy. The rotational barrier of 2,3′-diamino-6-(octanoyloxymethyl)biphenyl has been evaluated by HPLC and by dynamic NMR. The rotational barrier of 2,3′-diamino-6-(acetoxymethyl)biphenyl was evaluated by theoretical calculations and compared with the experimental data relative to its analogue. [Copyright &y& Elsevier]

[Display omitted] • Resveratrol glycoliposomes for Methicillin Resistant Staphylococcus aureus biofilm. • Galactosyl-amphiphile targets Methicillin Resistant Staphylococcus aureus biofilm. • Cationic galactosyl-amphiphiles enhance liposomes binding to biofilm. • Cationic galactosylated liposomes enhance resveratrol delivery to biofilm. Novel cationic glycoliposomes, composed of 1,2-dioleoyl- sn -glycero-3-phosphocholine (DOPC), cholesterol (Chol) and glycoamphiphiles featuring a galactosyl, mannosyl or glucosyl moiety have been investigated for the targeted delivery of trans -resveratrol (RSV), a Quorum Sensing Inhibitor (QSI), to Methicillin Resistant Staphylococcus Aureus (MRSA) biofilms. All the glycosylated formulations show a 10–20 % reduction of their hydrodynamic size and a high positive increase in ζ-potential (20÷27mV), with respect to the almost neutral DOPC/Chol liposomes (-3.7 mV). RSV is entrapped in liposomes with high Entrapment Efficiency (EE%), the formulations containing glycosylated amphiphiles showing higher values of EE% (79–90 %) than those containing DOPC/CHOL (65 %). In all the liposomal formulations, the inclusion of RSV causes a decrease in ζ-potential, which is particularly evident in the negative value of DOPC/Chol liposomes (-14.8 mV). This is probably due to the ionization of a small percentage of RSV molecules that point towards the lipid/water interface, as reported in the literature. Greater antioxidant activity is found when RSV is embedded in glycosylated liposomes, rather than DOPC/CHOL liposomes. This finding suggests a different RSV distribution in the lipid membrane enclosing the glycosylated amphiphiles, which favor an external exposure of RSV. Biological assays carried out to monitor the demolition effect of RSV-loaded liposomes on mature biofilm of MRSA show that the presence of cationic glycoamphiphiles is essential for a demolition effect to take place on the biofilm matrix. In particular, RSV-galactosylated liposomes are the most effective in destroying MRSA biofilm even at a RSV concentration (0.019 mM) sixty times lower than the MIC (1.2 mM). This work demonstrates, for the first time, how the functionalization of liposomes with cationic glycosydic residues can enhance liposome performances as QSI nanocarriers for the treatment of biofilm associated infections. [ABSTRACT FROM AUTHOR]

Three new fluorescent molecular rotors were synthesized with the aim of using them as sensors to dose thymidine phosphorylase, one of the target enzymes of 5-fluorouracil, a potent chemotherapic drug largely used in the treatment of many solid tumors, that acts by hindering the metabolism of pyrimidines. 5-Fluorouracil has a very narrow therapeutic window, in fact, its optimal dosage is strictly related to the level of its target enzymes that vary significantly among patients, and it would be of the utmost importance to have an easy and fast method to detect and quantify them. The three molecular rotors developed as TP sensors differ in the length of the alkylic spacer joining the ligand unit, a thymine moiety, and the fluorescent molecular rotor, a [4-(1-dimethylamino)phenyl]-pyridinium bromide. Their ability to trigger an optical signal upon the interaction with thymidine phosphorylase was investigated by fluorescent measurements. [ABSTRACT FROM AUTHOR]

• VOA loaded in liposomes can revert resistance of osteosarcoma cells to doxorubicine. • Liposomes bilayers differ for the fluidity (phospholipid component is DPPC or DOPC). • Liposomes formulations differ for the stereochemistry of the synthetic component. • Subtle variations of lipid molecular structure alter their interaction with cells. The plant alkaloid voacamine (VOA) displays many interesting pharmacological activities thus, considering its scarce solubility in water, its encapsulation into liposome formulations for its delivery is an important goal. Different cationic liposome formulations containing a phospholipid, cholesterol and one of two diasteromeric cationic surfactants resulted able to maintain a stable transmembrane difference in ammonium sulfate concentration and/or pH gradient and to accumulate VOA in their internal aqueous bulk. The fluidity of the lipid bilayer affects both the ability to maintain a stable imbalance of protons and/or ammonium ions across the membrane and the entrapment efficiency. It was shown that VOA loaded into liposomes is more efficient than the free alkaloid to revert resistance of osteosarcoma cells resistant to doxorubicin to an extent depending on their composition. [ABSTRACT FROM AUTHOR]