Linda Pastero

Cyclodextrin-based nanosponges encapsulating camptothecin: Physicochemical characterization, stability and cytotoxicity

Camptothecin (CAM), a plant alkaloid and a potent antitumor agent, has a limited therapeutic utility because of its poor aqueous solubility, lactone ring instability and serious side effects. Cyclodextrin-based nanosponges (NS) are a novel class of cross-linked derivatives of cyclodextrins. They have been used to increase the solubility of poorly soluble actives, to protect the labile groups and control the release. This study aimed at formulating complexes of CAM with three types of beta-cyclodextrin NS obtained with different cross-linking ratio (viz. 1:2, 1:4 and 1:8 on molar basis with the cross-linker) to protect the lactone ring from hydrolysis and to prolong the release kinetics of CAM. Crystalline (F(1:2), F(1:4) and F(1:8)) and paracrystalline NS formulations were prepared. XRPD, DSC and FTIR studies confirmed the interactions of CAM with NS. XRPD showed that the crystallinity of CAM decreased after loading. CAM was loaded as much as 21%, 37% and 13% w/w in F(1:2), F(1:4) and F(1:8), respectively while the paracrystalline NS formulations gave a loading of about 10% w/w or lower. The particle sizes of the loaded NS formulations were between 450 and 600nm with low polydispersity indices. The zeta potentials were sufficiently high (-20 to -25mV) to obtain a stable colloidal nanosuspension. The in vitro studies indicated a slow and prolonged CAM release over a period of 24h. The NS formulations protected the lactone ring of CAM after their incubation in physiological conditions at 37 degrees C for 24h with a 80% w/w of intact lactone ring when compared to only around 20% w/w of plain CAM. The cytotoxicity studies on HT-29 cells showed that the CAM formulations were more cytotoxic than plain CAM after 24h of incubation.

Encapsulation of Acyclovir in new carboxylated cyclodextrin-based nanosponges improves the agent's antiviral efficacy

Cyclodextrin-based nanosponges (NS) are solid nanoparticles, obtained from the cross-linking of cyclodextrins that have been proposed as delivery systems for many types of drugs. Various NS derivatives are currently under investigation in order that their properties might be tuned for different applications. In this work, new carboxylated cyclodextrin-based nanosponges (Carb-NS) carrying carboxylic groups within their structure were purposely designed as novel Acyclovir carriers. TEM measurements revealed their spherical shape and size of about 400 nm. The behaviour of Carb-NS, with respect to the incorporation and delivery of Acyclovir, was compared to that of NS, previously investigated as a drug carrier. DSC, XRPD and FTIR analyses were used to investigate the two NS formulations. The results confirm the incorporation of the drug into the NS structure and NS-Acyclovir interactions. The Acyclovir loading into Carb-NS was higher than that obtained using NS, reaching about 70% (w/w). In vitro release studies showed the release kinetics of Acyclovir from Carb-NS to be prolonged in comparison with those observed with NS, with no initial burst effect. The NS uptake into cells was evaluated using fluorescent Carb-NS and revealed the nanoparticle internalisation. Enhanced antiviral activity against a clinical isolate of HSV-1 was obtained using Acyclovir loaded in Carb-NS.

The competition between {} cleavage and {} steep rhombohedra in gel grown calcite crystals

Abstract Calcite crystals have been obtained from supersaturated solutions diffusing both in agarose and Na-metasilicate gels. Crystal morphology in agarose is characterized mainly by spherulites grown around solid gel impurities and terminated by the cleavage {1 0 1 4} rhombohedron. Grown from Na-metasilicate gel, {1 0 1 4} and {0 1 1 2} rhombohedra compete according to the influence of pH and of the acidifying agent, HCl or CH3COOH, the latter favouring the appearance of the {0 1 1 2} form.

Revisiting the paradigm of silica pathogenicity with synthetic quartz crystals: the role of crystallinity and surface disorder

BackgroundExposure to some - but not all - quartz particles is associated to silicosis, lung cancer and autoimmune diseases. What imparts pathogenicity to any single quartz source is however still unclear. Crystallinity and various surface features are implied in toxicity. Quartz dusts used so far in particle toxicology have been obtained by grinding rocks containing natural quartz, a process which affects crystallinity and yields dusts with variable surface states. To clarify the role of crystallinity in quartz pathogenicity we have grown intact quartz crystals in respirable size.MethodsQuartz crystals were grown and compared with a fractured specimen obtained by grinding the largest synthetic crystals and a mineral quartz (positive control). The key physico-chemical features relevant to particle toxicity - particle size distribution, micromorphology, crystallinity, surface charge, cell-free oxidative potential - were evaluated. Membranolysis was assessed on biological and artificial membranes. Endpoints of cellular stress were evaluated on RAW 264.7 murine macrophages by High Content Analysis after ascertaining cellular uptake by bio-TEM imaging of quartz-exposed cells.ResultsQuartz crystals were grown in the submicron (n-Qz-syn) or micron (μ-Qz-syn) range by modulating the synthetic procedure. Independently from size as-grown quartz crystals with regular intact faces did not elicit cellular toxicity and lysosomal stress on RAW 264.7 macrophages, and were non-membranolytic on liposome and red blood cells. When fractured, synthetic quartz (μ-Qz-syn-f) attained particle morphology and size close to the mineral quartz dust (Qz-f, positive control) and similarly induced cellular toxicity and membranolysis. Fracturing imparted a higher heterogeneity of silanol acidic sites and radical species at the quartz surface.ConclusionsOur data support the hypothesis that the biological activity of quartz dust is not due to crystallinity but to crystal fragmentation, when conchoidal fractures are formed. Besides radical generation, fracturing upsets the expected long-range order of non-radical surface moieties - silanols, silanolates, siloxanes - which disrupt membranes and induce cellular toxicity, both outcomes associated to the inflammatory response to quartz.

Polymorphic–polytypic transition induced in crystals by interaction of spirals and 2D growth mechanisms

The relationship between crystal polymorphism and polytypism can be revealed by surface patterns through the interlacing of the growth spirals. Simple high-symmetry structures as SiC, ZnS, CdI2 and more complex low-symmetry layered structures as n-paraffins, n-alcohols and micas are concerned with polymorphic–polytypic transition. In this paper, we will show for the first time, through in situ AFM observations and X-ray diffractometry, that a protein polymorph (P212121a-amylase) locally changes, during growth, to a monoclinic P21 polytype, thanks to the screw dislocation activity. The interplay between spiral steps and 2D nuclei of the polytypes coexisting in the same crystalline individual allows to foresee the consequences on the crystal quality. The discussion is extended to other mineral and biological molecules and a new general rule is proposed to explain the interactions between surface patterns and the bulk crystal structure. r 2002 Elsevier Science B.V. All rights reserved.

Bi-2212 and Y123 highly curved single-crystal-like objects: whiskers, bows and ring-like structures

High-temperature superconducting objects of Bi2Sr2CaCu2O8 and Y Ba2Cu3O7 highly curved in the ab-plane, such as curved/kinked whiskers, bows and ring-like structures, were obtained within a solid?liquid?solid (SLS) grass-like growth mechanism. As-grown objects are crystals with three-dimensional epitaxy similar to conventional single crystals: they can be viewed as crystal parts ?cut? from a conventional rectangular crystal. Between our curved objects and conventional crystals, whiskers or thin films there are some differences in the superconducting properties induced only by the shape factors and no new physics is observed. Some details of the growth mechanism are discussed, emphasizing curved-line formation.

Microwave‐Assisted Synthesis and Physicochemical Characterization of Tetrafuranylporphyrin‐Grafted Reduced‐Graphene Oxide

This work describes the design of a modified porphyrin that bears four furan rings linked by 1,2-bis-(2-aminoethoxy)ethane spacers. This unit is a well-suited scaffold for a Diels-Alder reaction with commercial reduced-graphene oxide, which is also described in this paper. A new hybrid material is obtained, thanks to efficient grafting under microwave irradiation, and fully characterized in terms of structure (UV, TGA, Raman) and morphology (HR-TEM and AFM). Potential applications in photo- and sonodynamic therapy are envisaged.

Digestion Procedures for the Elemental Analysis of Wood by Inductively Coupled Plasma Optical Emission Spectrometry

ABSTRACT Various digestion methods are available for the elemental analysis of wood biomass. Microwave digestion is the current European standard method for the determination of major and minor elements in solid biofuels. Because of the small masses (≤0.5 g) employed in microwave digestion, the resulting analyte concentrations in solution are low, and inductively coupled plasma mass spectrometry (ICP-MS) may be necessary to provide the required low limits of detection. However, higher concentrations are required for inductively coupled plasma optical emission spectrometry (ICP-OES) compared to ICP-MS. In this work, wet, dry, ash fusion, and microwave digestion were employed to determine Al, Ca, Fe, Mg, P, K, Si, Na, S, Cd, Co, Cr, Cu, Mn, Ni, Pb, and Zn in wood biomass by ICP-OES. Two certified reference materials (BCR 100, beech leaves and BCR 62, olive leaves) were used in this study. The concentrations of Cd, Co, Cr, Cu, Ni, and Pb were below the limits of quantification for ICP-OES. Wet digestion was suitable for the elemental analysis of wood biomass by ICP-OES with the exceptions of Al and Si. Dry digestion was accurate for some elements and ash fusion was the most accurate for the determination of silicon.

Calcite passivation by gypsum: the role of the cooperative effect

The overgrowth of gypsum (CaSO4·2H2O) on calcite (CaCO3), used as a substrate, has been obtained in order to verify the hypothesis of a crystallographic fit between the two phases. Lattice coincidences show that many orientations of gypsum with respect to calcite can occur. Experimentally, only two among these are fulfilled during the early stages of growth, the selection criterion reasonably being the adhesion energy. Moreover, it has been shown that the presence of calcium carbonate as a specific surface impurity in solution modifies the growth habit of gypsum acting on the growth rate and surface morphology of some gypsum forms. At high concentration, the calcium carbonate in solution promotes the twinning of gypsum according to the Montmartre law.

A novel layered aluminophosphate with corner-sharing AlO6chains

The synthesis, Raman spectroscopy and crystal structure of a novel layered aluminophosphate is described. The new phase was derived by the sol-gel method starting from a modified low hydrothermal ALPO4-34 zeolite synthesis procedure[1].The structure was solved by direct methods using single-crystal X-ray diffraction. The synthesized layered material, with composition [AlPO3(OH)F(H2O)](H9C4ON), crystallizes in the monoclinic space group P21/a with a = 9.2282(5) Å, b = 6.9152(4) Å, c = 14.4615(9) Å, β = 101.57(1)°. Layered aluminophosphates with AlO6 polyhedra have been previously described [2], although in these compounds Al octahedral share edges. The novel compound has corner sharing AlO4F(H2O) chains along [010], where fluorine is at the shared apex, four oxygen atoms are shared with PO4 tetrahedra and the fifth oxygen is a H2O group. This kind of aluminophosphate chains is found in nature in tancoite [3]. Chains are linked along [100] through corner sharing with a PO4 group of the adjacent chain plus hydrogen bonding of the H2O group. Layers are stacked along c* through hydrogen bonding with a double layer of morpholine (H9C4ON) molecules. The chemical stability field of the novel materialis strongly dependent from the fluorine/aluminum ratio of the starting gel. At lower fluorine concentrations only ALPO4-34 and/or AlPO4 (berlinite) are stable depending on the morpholine content. Crystals growth morphology depends on the supersaturation conditions of the starting gel: at low concentrations crystals are well developed hexagonal like plate shaped and are very thin. At higher concentrations they show a more elongated morphology. A treatment with H2CO3 leads to a complete morpholine removal, as shown by in situ Raman spectroscopy. Powder X-ray diffraction reveals that after morpholine extraction, the material diffract still coherently in two dimensions while a strong broadening is shown for basal planes.