Magnetic layered double hydroxides with carbamazepine for breast cancer treatment.

Current cancer chemotherapy is associated with many side effects and, in some cases, drug resistance, which makes the search for new active molecules and drug delivery strategies imperative. Carbamazepine is an antiepileptic compound that has shown efficacy against breast cancer cell lines. In this study, it was incorporated into layered double hydroxide nanoclays, the percentage of drug loading was increased compared to previous research, and the clays were impregnated with magnetic Fe3O4 nanoparticles. The goal of the magnetic Fe3O4-impregnation was to direct the nanocomposites to the therapeutic target with an external magnetic field. The nanoclay-carbamazepine composites had a carbamazepine loading of 51 %, and the nanoclay-carbamazepine-nanoparticles had a drug loading of 13 % due to the addition of more ingredients. The structure of the composites was analyzed by X-ray diffraction and Scherrer equation, showing a layered double hydroxide organization with crystal sizes of 9-15 nm; from transmission electron microscopy, the final compounds showed a particle size of 97-158 nm, small enough for systemic circulation. In vibrating sample magnetization studies, the composites showed a superparamagnetic behavior with high magnetic saturation (9-17 emu/gr), which should allow a good material attraction by an external magnetic field located near the tumor. In vitro drug release studies were done in Franz cells and measured by UV/Vis spectrophotometry; they showed that carbamazepine release from the nanocomposites responds to the media pH: a good drug release at the lysosome pH and slow release at the blood pH. Finally, the efficacy was tested in vitro in MDA-MB-231 breast cancer cells, and the composites showed an enhanced efficacy in comparison with that produced by the free drug (96 % and 62 % of cell inhibition respectively). Carbamazepine administered with magnetic clays as a carrier is a promising treatment for breast cancer, and further studies should be done to measure the arrival time and the efficacy in vivo.

Assessing the Adjuvant Effect of Layered Double Hydroxides (LDH) on BALB/c Mice.

The discovery and validation of new adjuvants are critical areas for vaccinology. Mineral materials (e.g., alum microparticles) have been used for a long time as adjuvants in human vaccine formulations. Nonetheless, the use of nanosized materials is a promising approach to diversify the properties of adjuvants. Nanoclays are potential adjuvants proposed by some research groups. However, their adjuvant mechanisms and safety have not been fully elucidated. Herein, we aimed at expanding the knowledge on the potential adjuvanticity of layered double hydroxide (LDH) nanoparticles by reporting a detailed method for the synthesis and characterization of LDHs and the adsorption of a model antigen (bovine serum albumin, BSA). LDHs varying in diameter (from 56 to 88 nm) were obtained, and an in vitro evaluation revealed that the LDHs are not inherently toxic. BSA was passively adsorbed onto the LDHs, and the immunogenicity in mice of the conjugates obtained was compared to that of free BSA and BSA co-administered with alum (Alum-BSA). The LDH-BSA conjugates induced a higher humoral response that lasted for a longer period compared with that of free BSA and Alum-BSA, confirming that LDH exerts adjuvant effects. The 56 nm LDH particles were deemed as the more efficient carrier since they induced a higher and more balanced Th1/Th2 response than the 88 nm particles. This study is a contribution toward expanding the characterization and use of nanoclays in vaccinology and justifies further studies with pathogen-specific antigens.

Effects of a lycopene-layered double hydroxide composite administration in cells and lungs of adult mice.

Lycopene is a natural compound with one of the highest antioxidant activities. Its consumption is associated with lower risks in lung cancer and chronic obstructive pulmonary disease, for example. Experimentally, a murine model demonstrated the ingestion of lycopene, which reduced the damage in lungs caused by cigarette smoke. Since lycopene is highly hydrophobic, its formulations in supplements and preparations for laboratory assays are based on oils, additionally, bioavailavility is low. We developed a lycopene layered double hydroxide (Lyc-LDH) composite, which is capable of transporting lycopene aqueous media. Our objective was to evaluate the cytotoxicity of Lyc-LDH and the intra-cellular production of reactive oxygen species (ROS) in J774A.1 cells. Also, in vivo assays were conducted with 50 male C57BL/6 mice intranasally treated with Lyc-LDH 10 mg/kg (LG10), Lyc-LDH 25 mg/kg (LG25) and Lyc-LDH 50 mg/kg (LG50) during five days compared against a vehicle (VG) and control (CG) group. The blood, bronchoalveolar lavage fluid (BALF) and lung tissue were analyzed. The results revealed that Lyc-LDH composite attenuated intracellular ROS production stimulated with lipopolysacharide. In BALF, the highest doses of Lyc-LDH (LG25 and LG50) promoted influx of macrophages, lymphocytes, neutrophils and eosinophils compared to CG and VG. Also, LG50 increased the levels of IL-6 and IL-13, and promoted the redox imbalance in the pulmonary tissue. On the contrary, low concentrations did not produce significative effects. In conclusion, our results suggest that intranasal administration of high concentrations of Lyc-LDH induces inflammation as well as redox status changes in the lungs of healthy mice, however, results with low concentrations open a promising way to study LDH composites as vehicles for intranasal administration of antioxidant coadjuvants.

Insights into the Preparation of Copper Catalysts Supported on Layered Double Hydroxide Derived Mixed Oxides for Ethanol Dehydrogenation.

Acetaldehyde is an important chemical commodity and a building block for producing several other high-value products in the chemical industry. This has motivated the search for suitable, efficient, stable, and selective catalysts, as well as renewable raw materials such as ethanol. In this work, supported copper catalysts were prepared from CuZnAl layered double hydroxides (LDHs) with different copper contents (5, 10, and 20 wt %) for application in the ethanol dehydrogenation reaction (EDR). The samples were thoroughly characterized by a series of techniques, which allowed for analysis of all of the copper and zinc species involved in the different catalyst preparation steps and during the EDR. The results obtained by in situ quick extended X-ray absorption fine structure (EXAFS) measurements, combined with multivariate data analysis, showed that the copper content in the pristine LDH influenced the phase composition of the mixed oxide support, which consequently affected the dispersion of copper nanoparticles. The higher the copper content, the higher are the ZnAl2O4 and zinc tetrahedral prenuclei (TPN) contents, to the detriment of the ZnO content. All the samples showed high selectivity (>97%) and stability in the catalytic reactions at 300 and 350 °C, with no observed deactivation during 6 h on-stream. Although the samples with lower copper content presented higher copper dispersion and reactivity, the sample containing 20 wt % of copper outperformed the others, with greater conversion and higher activity toward acetaldehyde.

New nanocarried phenobarbital formulation: Maintains better control of pentylenetetrazole-Induced seizures.

This study aims to evaluate the efficacy of slow release phenobarbital in the control of convulsions triggered by pentylenetetrazole (PTZ), verifying the time of permanence in the anticonvulsant effect through behavior and electroencephalographic records. A total of 162 male Wistar rats weighing between 100 and 120 g were divided into two groups, one for behavior analysis (n = 90) and biochemistry, and another for the acquisition of electrocorticographic record (n = 72). Hepatic enzymes were measured by obtaining a blood sample from the animals studied by means of a biochemical analysis. The procedures for electrode implant and electrocorticographic recordings were performed. The intercalation of phenobarbital in layered double hydroxide (LDH) nanocarrier allowed us to evaluate a new slow release pharmaceutical formulation based on methodologies that have proven longer residence time and lower side effects. This study demonstrates that phenobarbital can be a new perspective pharmaceutical formulation.

Room temperature and aqueous synthesis of bimetallic ZIF derived CoNi layered double hydroxides and their applications in asymmetric supercapacitors.

Single imidazolate framework-67 (ZIF-67) is commonly used as a template to prepare layered double hydroxides (LDHs) with specific morphology to improve the performance of materials. Herein, the Co2+ ion in ZIF-67 is partially substituted by Ni2+ to obtain the dodecahedron bimetallic imidazolate framework (CoNi-ZIF). Subsequently, using bimetallic CoNi-ZIF as the sacrificial template, CoNi-LDH hierarchical hollow cage structures with wrinkled nanosheet arrays are synthesized at room temperature and in aqueous solution by an inexpensive and environment friendly surfactant-free approach. The optimized etched CoNi-LDH4 has a maximum specific capacitance of 1877 F g-1 at a current density of 1 A g-1, and cycling stability of 99.89% after 5000 cycles, which is significantly better than that of ZIF-67 derived CoNi-LDH67 (1357 F g-1 at 1 A g-1, cycling stability of 73.35%). The asymmetric supercapacitor with CoNi-LDH4 as a cathode and activated carbon (AC) as anode has an energy density of 49.3 Wh kg-1 at 750 W kg-1 power output and stable cycling performance (capacity retention of 92.13% after 5000 cycles). This study shows the prospect of bimetallic CoNi-ZIF derived LDHs nanostructures prepared at room temperature and in aqueous solution to improve the performance and stability of supercapacitors.

Adsorption of organic and inorganic arsenic from aqueous solutions using MgAl-LDH with incorporated nitroprusside.

An evaluation was made of the use of MgAl-LDH with incorporated nitroprusside as an adsorbent to remove inorganic arsenic (As(III) and As(V)) and organic arsenic (DMA) from aqueous matrices. The material was synthesized by the co-precipitation method at constant pH and was characterized by Raman spectroscopy, infrared spectroscopy, thermogravimetry, X-ray diffraction, and high-resolution transmission electron microscopy, before and after use in the adsorption process. The effects on adsorption of contact time, initial metalloid concentration, and pH were investigated. For an initial concentration of 10 mg L-1 and pH 2.00, the MgAl-LDH with incorporated nitroprusside was only able to adsorb the DMA and As(V) species, with removal percentages of 25.10 and 103.8%, respectively. At pH 6.02 and 12.00, only the inorganic species were adsorbed, with removal percentages of 22.93% and 60.07%, respectively, for As(III), and 89.81% and 71.64%, respectively, for As(V). Application of the Langmuir and Freundlich isotherm models indicated that the features of the adsorption process depended on the pH of the medium and the arsenic species. The results showed that the use of MgAl-LDH with incorporated nitroprusside has potential for the development of techniques for the speciation of arsenic species.

Folate- and glucuronate-functionalization of layered double hydroxides containing dysprosium and gadolinium and the effect on oxidative stress in rat liver mitochondria.

Zinc/aluminum layered double hydroxide (LDH) particles were prepared by alkaline precipitation in the presence of dysprosium and dysprosium/gadolinium cations. The particles formed were stable against exchange reactions with folate or glucuronate ions since these organic ions exclusively functionalized the external surface of the layered double hydroxides. While the dysprosium derivatives reached magnetization susceptibilities between 2.06 × 10-5 and 2.20 × 10-5 cm3/g, the samples simultaneously containing dysprosium and gadolinium decreased to a range between 1.08 × 10-5 and 1.73 × 10-5 cm3/g. This last sample was tested as a magnetic resonance imaging contrast agent and demonstrated a reduction in T1 and T2 relaxation times in a linear dependence with the LDH concentration. The oxidative stress assays in rat liver mitochondria demonstrated the low toxicity of the composition simultaneously containing dysprosium and gadolinium as well as the functionalization product with glucuronate ions, suggesting the potential of these particles to design alternative MRI contrast agents.

Removal and Extraction of Carboxylic Acids and Non-ionic Compounds with Simple Hydroxides and Layered Double Hydroxides.

Carboxylic acids are an important natural component as a final product or intermediates for syntheses. They are produced in plants, animals and also as products from biotechnological processes. This review presents the use of single hydroxide particles and layered double hydroxides as alternative adsorbents to remove carboxylic acids from liquid media. The proposal to use hydroxide particles is based on its affinity to adsorb or intercalate carboxylic acids. Besides, the change in properties of the adsorbate-sorbate product evinces that this intermediate can be used as a vehicle to transport and release carboxylic acids. Additional examples will also be presented to prove that layered hydroxides are capable of removing non-ionic compounds from wine, milk and tomato. The use of layered compounds to remove active ingredients could reduce the number of separations steps, costs and reduce or eliminate solvents, thus encouraging the design of industrial processes of separation using hydroxides particles.

Enhanced apoptosis and inhibition of gastric cancer cell invasion following treatment with LDH@Au loaded Doxorubicin

Background: The suppression of cancer cell growth and invasion has become a challenging clinical issue. In this study, we used nanotechnology to create a new drug delivery system to enhance the efficacy of existing drugs. We developed layered double hydroxide by combing Au nanosol (LDH@Au) and characterized the compound to prove its function as a drug delivery agent. The anti-cancer drug Doxorubicin was loaded into the new drug carrier to assess its quality. We used a combination of apoptosis assays, cell cycle assays, tissue distribution studies, cell endocytosis, transwell invasion assays, and immunoblotting to evaluate the characteristics of LDH@Au as a drug delivery system. Results: Our results show that the LDH@Au-Dox treatment significantly increased cancer cell apoptosis and inhibited cell invasion compared to the control Dox group. Additionally, our data indicate that LDH@Au-Dox has a better target efficiency at the tumor site and improved the following: cellular uptake, anti-angiogenesis action, changes in the cell cycle, and increased caspase pathway activation. Conclusions: Our findings suggest the nano drug is a promising anti-cancer agent and has potential clinical applications.

Influence of buffer solutions in the adsorption of human serum proteins onto layered double hydroxide.

The adsorption of human immunoglobulin G (IgG) and human serum albumin (HSA) on a non-calcined Mg-Al layered double hydroxide (3:1 Mg-Al LDH) was studied in batch and fixed bed experiments, focusing on the effect of buffer solution and pH over sorbent uptake. Mg-Al LDH was synthesized and characterized by X-ray diffraction (XRD), N2 adsorption-desorption isotherms at -196°C, X-ray photoelectron spectroscopy (XPS), Zero point charge (pHzpc), particle size distribution and Fourier transform infra-red (FTIR). Batch adsorption experiments were performed in order to investigate the effects of pH on IgG and HSA adsorption with different buffers: sodium acetate (ACETATE), sodium phosphate (PHOSPHATE), 3-(N-morpholino) propanesulfonic acid (MOPS), 4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid (HEPES) and trizma-hydrochloric acid (TRIS-HCl). Maximum adsorption capacities estimated by the Langmuir model were 239mgg-1 for IgG and 105mgg-1 for HSA in TRIS-HCl buffer. On the other hand, the highest selectivity for IgG adsorption over HSA was obtained with buffer PHOSPHATE (pH 6.5). The maximum IgG and HSA adsorption uptake in this case were 165 and 36mgg-1, respectively. Fixed bed experiments were carried out with both proteins using PHOSPHATE buffer (pH 6.5), which confirmed that IgG was more selectively adsorbed than HSA on Mg-Al LDH and both could be fully recovered by elution with sodium chloride (NaCl).

Selective oxidation catalysts obtained by immobilization of iron(III) porphyrins on thiosalicylic acid-modified Mg-Al layered double hydroxides.

Nitrate-intercalated Mg-Al layered double hydroxides (LDHs) were synthesized and exfoliated in formamide. Reaction of the single layer suspension with thiosalicylic acid under different conditions afforded two types of solids: LDHA1, in which the outer surface was modified with the anion thiosalicylate, and LDHA2, which contained the anion thiosalicylate intercalated between the LDH layers. LDHA1 and LDHA2 were used as supports to immobilize neutral (FeP1 and FeP2) and anionic (FeP3) iron(III) porphyrins. For comparison purposes, the iron(III) porphyrins (FePs) were also immobilized on LDH intercalated with nitrate anions obtained by the co-precipitation method. Chemical modification of LDH facilitated immobilization of the FePs through interaction of the functionalizing groups in LDH with the peripheral substituents on the porphyrin ring. The resulting FePx-LDHAy solids were characterized by X-ray diffraction (powder) and UV-Vis and EPR spectroscopies and were investigated as catalysts in the oxidation of cyclooctene and cyclohexane. The immobilized neutral FePs and their homogeneous counterparts gave similar product yields in the oxidation of cyclooctene, suggesting that immobilization of the FePs on the thiosalicylate-modified LDHs only supported the catalyst species without interfering in the catalytic outcome. On the other hand, in the oxidation of cyclohexane, the thiosalicylate anions on the outer surface of LDHA1 or intercalated between the LDHA2 layers influenced the catalytic activity of FePx-LDHAy, leading to different efficiency and selectivity results. FeP1-LDHA2 performed the best (29.6% alcohol yield) due to changes in the polarity of the surface of the support and the presence of FeP1. Interestingly, FeP1 also performed better in solution as compared to the other FePs. Finally, it was possible to recycle FeP1-LDHA2 at least three times.

Delivery system for mefenamic acid based on the nanocarrier layered double hydroxide: Physicochemical characterization and evaluation of anti-inflammatory and antinociceptive potential.

PURPOSE: The anionic form of the drug mefenamic acid intercalated into the nanocarrier layered double hydroxide (LDH-Mef) was evaluated by anti-inflammatory and antinociceptive assays. METHODS: The LDH-Mef material was characterized by a set of physicochemical techniques, which was supported by Density Functional Theory calculations. The pharmacological effects of LDH-Mef (40 wt% of drug) were evaluated by hemolytic, anti-inflammatory activity and antinociceptive assays. RESULTS: In vivo assays were conducted for the first time in order to assess the LDH-Mef potential. The hemolytic effects decreased for the intercalated Mef as demonstrated by the higher tolerated hemolytic concentration (1.83 mM) compared to mefenamic acid (MefH), 0.48 mM. Pretreatment of animals with MefH or LDH-Mef reduced carrageenan-, dextran sulfate- and PGE2-induced paw edema. MefH or LDH-Mef also decrease total leucocytes and neutrophil counts of the peritoneal cavity after inflammation induction with carrageenan. In the nociception model, oral pretreatment with LDH-Mef reduced mechanical hypernociception carrageenan-induced after 3-4h and also the number of writhings induced by acetic acid. CONCLUSIONS: This work shows the increase of the anti-inflammatory and antinociceptive potential of the drug confined into the LDH, as well as, its hemolytic effect.