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What is critical for allergy prevention in early life?
Allergy rates including eczema and food allergy in Australia are amongst the highest in the world affecting those with or without a family history of allergy. Preventive strategies are paramount to lower the ever-rising statistics. However, previously recommended practices, such the avoidance of food allergens, do not seem to have reduced the burden of allergic disease and may have made the situation worse. We now see mounting evidence from randomised studies showing that early exposure is critical for allergy prevention and the recently updated Australasian Society of Clinical Immunology and Allergy guidelines for infant feeding and allergy prevention now aim to support the four to six months of age for commencing solids.
Strategies around the first 1,000 days from conception to early infancy are critical to support healthy immune development and breast feeding remains the gold standard for infant feeding. A healthy diet throughout pregnancy, the timing of the introduction of complementary foods along with adequate vitamin D status are also key.
Diversity of the microbiome is an important concept to consider as the clinical decisions we make can have consequences for the infant microbiome and hence immune development. The method of delivery, the use of maternal and neonatal antibiotics, if breast fed or formula fed, can modify the microbiome and affect the immune system long term. If the baby cannot breast feed, then the addition of pre and probiotics into infant formula or as a supplement is becoming more relevant with recent recommendations from the World Allergy Organisation.
Article submitted by Dr John Sinn, Paediatric Allergist and Neonatologist


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Document Type: Review Paper
Chemistry Department, Institute of Nanotechnology, Razi University, Kermanshah, Iran
Direct delivery of drugs and bioactive molecules does not lead to appropriate therapeutic results and suffers from the main difficulties like poor bioavailability, enzymatic degradation, adverse drug reaction owing to great dosage and toxicity due to positional accumulation etc.[1]. Therefore, the search for efficient and safe transport vehicles-carriers were a challenging yet very exciting area of research in recent years and is going to be of interest for many years to come [2]. Among all nanocarriers which applied as drug delivery vectors, layered double hydroxides (LDHs) with exchangeable anions in the positive brucite-like interlayers have been attracting much attention in the field of cellular delivery of anionic drug and other bio-functional molecules, due to their low toxicity, biocompatibility, high stability, pH dependent solubility and enhanced cellular uptake behavior compared with the conventional drug carriers [3]. For instance, clay minerals can act as transport vehicles/carriers for the efficient delivery of therapeutic molecules (drugs and genes) by modifying the rate and/or time of release, increasing the stability of the drug or improving the dissolution profile of a drug [4]. The LDHs have been known for many decades as a catalyst and ceramic precursors, traps for anionic pollutants, catalysts and additives for polymers, but their successful synthesis on the nanometer scale a few years ago opened up a whole new field for their application in nanomedicine [5]. The LDHs are available as naturally occurring minerals and as synthetic materials. They were first prepared in the laboratory in 1942 when Feitknecht reacted dilute aqueous metal salt solutions with base, although the first detailed structural analyses of LDHs were not carried out until the late 1960s by Allmann and Taylor and their co-workers [6]. The LDHs have many applications in various fields such as drug delivery, catalysis [7], wastewater treatment [8], cosmetic, etc. Particularly, in the pharmaceutical section, they are employed as (i) drug delivery systems [9-11], (ii) host materials for poorly soluble active pharmaceutical ingredients (APIs) [12, 13] (iii) rheological agents for topical formulations [14, 15]. These layered nanostructures consist of interlayer region containing charge compensating anions and solvation molecules. The metal cations occupy the centers of edge sharing octahedral, whose vertexes contain hydroxide ions that connect to form infinite 2D sheets. The most widely studied LDHs contain both divalent and trivalent metal cations, a generic formula for these LDHs may be written as; [M2+1−xM3+x (OH) 2] [An−] x/n·zH2O, where M2+ may be common; Mg2+, Zn2+, or Ni2+ and M3+ may be common; Al3+, Ga3+, Fe3+, or Mn3+. An− is a non-framework charge compensating inorganic or organic anion, e.g. CO32−, Cl−, SO42−, RCO2−, and x is normally between 0.2-0.4 [16-18]. Various methods have been developed to prepare LDHs with different sizes, including co-precipitation of inorganic salts in basic solution at either low or high super saturation, hydrothermal synthesis, reconstruction, and ion-exchange methods. There are two typical co-precipitation processes based on operation: (1) co-precipitation at high super-saturation, in which typically an M2+ and M3+ containing solution is added to a basic solution with the desired interlayer containing anions and the reaction is stopped when reaching a set pH value; (2) co-precipitation at low super saturation, in which two solutions, one containing construction metal cations and the other containing counter anions and a precipitation base are mixed together drop by drop [19]. In the last decades, passive diffusion was shown to be the main mechanism in drug transport across biological barriers, it is a key determinant in pharmacokinetics. Later studies showed carrier mediated process in drug transport across the biological membrane also played major roles, adding to the existing passive mechanism [20]. Common organic-based DDS include polymers (such as polysaccharides, chitosan, amphiphilic block copolymers block copolymer micelles, cellulose, hydrogels), lipid particles (micro emulsions), and a few natural particulates (pathogens and mammalian). Organic-based DDS have some disadvantages such as high toxicity, low loadings and easy leakage of drugs which reduce their drug-delivering efficiency [21]. Drug carriers based on inorganic nanomaterials, such as silica materials, show much better properties than organic carriers, including ease of controlled synthesis and environmental friendliness. The recently developed organic-inorganic nanohybrids based DDS such as LDH-chitosan hybrid or enteric polymer show good biocompatibility and avoid the drug leaching, but endure the difficulty of artificial synthesis, ordered structure, and industrial scale-up [22]. In this review, we collect the information published, roughly from 2001, on the intercalation of various drugs in different LDHs, as well as their controlled release. Furthermore, this review aims to report and examine the latest developments in LDH nanoparticles as efficient drug delivery systems (DDS) and to provide an outlook on possible future progress in this research area as well as some likely challenges that could be encountered.
Layered double hydroxides (LDH) Materials
The LDHs (Fig. 1) have a wide range of chemical compositions and their layer structure exhibits a variety of stacking faults to generate many different poly types. They exhibit various
particle sizes according to the synthetic route while the surface area values are generally lower than 100 m2 g−1. They also possess higher layer charge densities (2-5 meq g-1), which results in strong electrostatic forces between the brucite-type sheets and the anions, thus swelling is more difficult than for clay minerals. LDHs particularly prefer multivalent anions within their interlayer space due to strong electrostatic interaction and therefore LDHs bearing monovalent anions like nitrate or chloride ions are good precursors for exchange reactions [23].
LDH family belongs to the 2-D layered materials displaying a low dimensional opened structure that favors intercalation and adsorption processes with a large variety of organic species ranging from molecules to macromolecules and bio macromolecules [24]. The LDH also referred as anionic clays are based on the stacking of brucite like layers, in which part of the divalent cations (M2+) is replaced by the trivalent ones (M3+). By virtue of their remarkable surface area to mass ratio, highly efficient drug loading can be achieved with atomically thin 2D structures [5].
The LDH nanoparticles have been explored widely owing to their biocompatibility, as well as biodegradability in the biomedical field for cancer treatment, termed nano oncology. These inorganic layered solids are stable and have the ability to encapsulate or immobilize various bio- and organic molecules in the interlayer space [25]. By the way, the core@LDH nanostructure is an effective carrier for drug delivery purposes.
Today, several methods have been developed for the synthesis of LDHs. These include co-precipitation, the sol-gel method, direct deposition and the urea method. Each method has its own unique advantages and disadvantages when compared to the other methods. LDH nanoparticles also applied as the shell of the structure of carriers with different cores. The core@LDH nanocomposites are equipped not only with the unique physicochemical properties (e.g. nanometer size and layered structure), but also with new and interesting functions
(e.g. Magnetism, porous structure, and high surface-to-volume ratio). We will summarize the synthesis strategy and morphology of the core@LDH nanocomposites, and their applications in drug delivery.
These nanocomposites were prepared by different methods. The co-precipitation method is the simplest and, the most commonly used of all methods for the preparation of LDHs. This method involves the preparation of two solutions, the first containing the desired metal cations as salts (usually of chloride or nitrate) dissolved in solution in their desired stoichiometric ratio; and the second solution is a caustic solution at a pH of 9 or greater [26]. The caustic solution may also contain the desired interlayer anions depending on the co-precipitation method chosen. The LDH is then prepared by delivering the two solutions to each other dropwise from a burette, separating funnel or a peristaltic pump. The metal cations will co-precipitate, and then the solution reaches super saturation. Super saturation is achieved by the addition of the caustic solution which causes the solution pH to increase. When the solution pH exceeds the pH at which the most soluble hydroxide of the metals in solution is precipitated the LDH will precipitate [27]. The precise identity of the base is not particularly important, however, anions such as OH- may be competitively intercalated into the interlayer of the LDH. Once the solutions are combined the hydrotalcite will form as a precipitate that can be collected by filtration. The precipitate must be dried to remove excess water and ground to a uniform consistency before it can be used. The co-precipitation method is often preferred as it is simple to carry out and does not require any volatile solvents or other harsh and expensive chemicals or apparatus. Unfortunately, LDHs prepared by co-precipitation often suffer from poor crystallinity and the presence of impurities. In contrast a method like the urea method (which is in many ways similar to co-precipitation) allows better control of particle size and higher crystallinity than other methods. However, the urea method is only suitable for preparation of LDHs with high charge density, meaning it cannot be used to prepare LDHs containing Cu2+ or Cr3+[28].
Co-precipitation is a facile and commonly used method for synthesizing the LDH shell. The cores that have been widely studied include silica nanospheres, metal oxide nanoparticles and nanowires, and the shells produced by co-precipitation are always LDH nanoparticles. In general, the core adsorbs two different metal cations that subsequently precipitate on the surface of the core, and the LDH crystal growth occurs with aging at a certain temperature or through hydrothermal treatment (Fig. 2A). Zhang et al. used the co-precipitation method to prepare an anti-inflammatory drug-loaded LDH shell on the magnesium ferrite core. In this work the magnesium ferrite particle core that first adsorbed Mg2+ and Al3+ cations was mixed with a solution containing sodium hydroxide and diclofenac or ibuprofen to precipitate [29] .The ultrasound-assisted co-precipitation method has also been applied to synthesis a variety of core@LDH nanocomposites, such as SiO2@LDH, Fe3O4@LDH, and Y2O3:Er3+,Yb3+@SiO2@LDH [30].
Another common method which was applied more than other synthesis method in order to prepare LDH, is sol-gel. The first sol-gel method to fabricate LDH shells was reported by Wei and co-workers in 2010. In this method, the boehmite (AlOOH) primer sol prepared by hydrolyzing the precursor Al(OPr)3 was deposited on the scaffold (i.e. paper, cloth or sponge) with several cycles of sol-gel deposition (Fig. 2C). The generated AlOOH coating as both substrate and source of aluminum resulted in LDH in situ growth on the scaffold (Fig. 2C). Using this method, Wang, J., et al. (2014) successfully synthesized SiO2@LDH and Fe3O4@SiO2@LDH core–shell composites with diameters of ~600 nm and ~900 nm, respectively. Based on the SiO2@LDH core–shell structure and the sol-gel method, the same group also synthesized a SiO2@LDH yolk–shell and hollow structure by adjusting the concentration of urea. Using the sol-gel method, Wang et al. coated a much smaller SiO2 core (50 nm, compared with Wei et al.'s 340 nm) with LDH and generated SiO2@LDH core-shell nanocomposites. The sol-gel method can also be applied to grow LDH on the carbon coated Fe3O4, but failed to produce well-dispersed, homogenous core-shell particles [31].
One of the new synthesis methods to prepare LDH is direct deposited. In the direct deposition approach, the core material and LDH nanoparticles or nanosheets are synthesized separately, and subsequent combination of these building blocks generates a core-shell structure of self-assembling, followed by some post-treatment (Fig. 2D) [32]. MgAl-NO3 LDH was first delaminated in formamide to make a colloid solution with exfoliated LDH nanosheets. Polystyrene (PS) beads were dispersed in a formamide suspension containing LDH nanosheets, the suspension was then ultrasonically agitated to promote the adsorption of the LDH nanosheets onto the PS surface. The sample was recovered by centrifugation (6000 rpm, 30 min) washed with ultrapure water and then dispersed in an aqueous solution of PSS. Core-shell composites coated with multilayer shells of (PSS/LDH) were synthesized by repeating this procedure 20 times.
The so-called "urea hydrolysis method" is suitable for precipitation of various metal hydroxides. Ammonium and carbonate are released during decomposition of urea, see equations 1-4 below. The hydrolysis of urea can easily be controlled by controlling the temperature. The rate constant increases by about 200 times when the temperature is increased from 60 to 100 °C [20]. Oxidation states of the metal cations can be controlled by addition of oxidizing agents such as, ammonium persulfate. Typically, the pH of the solution is controlled to be in the area of pH = 6-10, which is where precipitation of most LDHs will occur. The urea method favors growth of larger particles than the earlier mentioned co-precipitation method. The urea method, consequently yields products with much higher crystallinity [33]. A disadvantage is that the formation of LDHs with the urea method will nearly just give carbonate as the interplay anion because of its high affinity for carbonate. According to Inayat et al. the decomposition of urea in aqueous solution to carbonate and hydroxide takes place in the following reaction steps:
CO (NH2)2 (aq) + H2O (l) → CO2 (aq) + 2NH3 (aq) (1)
NH3 (aq) + H2O (l) ⇄ NH4+ + OH- (aq) (2)
CO2 (aq ) + OH-(aq) ⇄ HCO3-(aq) (3)
HCO3-(aq) + OH-(aq) ⇄ CO32-(aq) + H2O (l) (4)
Recently, there has been reported a successful use of the urea method for direct synthesis of LDHs with nitrate as the interlayer anion. By carefully controlling the pH of the solution and by addition, excess nitrate, the intercalation of interlayer anion can be manipulated to other interlayer anions such as nitrate as well. The key parameter to control is the final pH of the synthesis mixture which are correlated to the initial nitrate/urea molar ratio and the synthesis time. By addition of ammonium nitrate to the reaction mixture, it is also possible to synthesize pure nitrate phase LHDs. Transition of pure phase of nitrate occurs at conditions pH < 7, via a mixed phase at pH = 7, to pure carbonate LDH at pH >7 [34].
Biological and pharmaceutical application of LDHs
The properties which make the LDHs useful in pharmaceutical applications are the high adsorption ability, high internal surface area, high cation-exchange capacity, interlayer reactions, chemical inertness, and low or null toxicity [35]. Nanostructured LDHs can serve as drug DDS, which exhibit the long-term stability and storage of the drug by isolating it from a hostile environment [36]. Depending on the field of applications, a large variety of LDH layer compositions have been studied ranging from MgAl, ZnAl, NiAl, MgFeAl to MgFe. Similarly, various intercalated anions have been tested, including inorganic anions (Cl-, NO3-, CO32-), organic surface modifiers (oleate, laurate, stearate, humic acid) but also functional organic species such as anticancer drugs, antibiotics and metal complexes [37].
Recently, considerable attention has been focused on the intercalation of biomolecules into LDHs. In addition to pharmaceuticals and enzymes which are discussed in more detail below, these include amino acids and peptides, vitamins, DNA and other nucleosides, ATP, and polysaccharides such as alginate, chitosan and carrageenan [38] .
Choy and co-workers (2002) have demonstrated that nanosized LDHs can be effective delivery carriers for drugs and genes by hybridization with DNA and antisense oligonucleotide
(As-myc). A strong suppression of cell growth (65%) was observed when HL-60 leukemia cells were incubated with 20 mM (As-myc)-LDH hybrid. The LDH itself was found to be non-cytotoxic against HL-60 cells. Consequently, LDHs can act as a new type of inorganic carrier that is completely different from existing non-viral vectors in terms of its chemical bonding and structure [39]. It is necessary to test cytotoxicity of LDHs themselves in the cells for use as antisense oligonucleotide delivery carrier. In fact, one critical element for the overall transfection efficacy of an oligonucleotide delivery system is cytotoxicity. Cell damage resulting from a cytotoxic delivery system is deleterious because following delivery, the cell must be capable of supporting translation and transcription. As shown in Fig. 3, LDHs themselves have no effect on the viability of HL-60 cells, the human promyelocytic leukemia cell, when administered at levels below 1000 μg mL-1 for up to 4 days. However, many cationic lipid complexes previously examined were bound to be toxic to cells at concentrations near their effective doses if exposure times were extended to several hours, suggesting that the molecules could not easily be metabolized [40].
Gene therapy is gaining attention for treatment of genetic deficiencies and life-threatening diseases. For the efficient introduction of foreign DNA into cells, a carrier system is required. Both viral and non-viral vectors are presently under research. Generally, nonviral vectors, consisting of a targeting ligand and a DNA-binding moiety, have great potential for gene therapy due to their safety, simplicity, and capacity for packaging very large DNA molecules. The major limiting factor in the development and application of these vectors has been poor transfection efficiency due, primarily, to endosomal degradation [39].
Recent research showed nanobiohybrids as a novel gene and DDS. Leroux et al. (2005), reported the formation of Mg-Ga LDH-DNA nanohybrids using the co-precipitation method. This "self-assembly" approach enabled the incorporation of long DNA fragments. X-ray diffraction analyses indicated a parallel orientation of the DNA double helices in the interlamellar space with respect to the hydroxide sheets. The presence of adsorbed DNA macromolecules also inhibited the crystal growth: hydrodynamic diameter measurements revealed homogeneous populations of particles with a mean diameter ranging from 90 to 150 nm, compatible with cell penetration through endocytosis. Concerning the surface charges of this new DNA delivery system, zeta-potential measurements indicated negative values between −20 and 40 mV which suggest incomplete DNA intercalation. Nevertheless, this low negative surface charge might be suitable for protecting DNA from extra-cellular degradations without preventing cell penetration [41].
Application of LDHs in drug delivery systems
Drug release is an important phenomenon in the field of drug delivery and it refers to the process by which the drug solutes migrate from the initial position in the delivery system to the outer surface of the same and henceforward to the release medium [42]. The important factor in drug-delivery systems is their affinity to release the active agents (drugs/biomolecules/genes, etc.) in a constant manner at the target location. The tendency of LDHs to release the drug in a sustained manner in a particular pH makes them superior from other DDSs. The drug release from LDH can be in a two-phase manner, initially, fast followed by a slower release. In addition, LDHs are able to concentrate selectively and organize organic molecules [43].
Profiting from the biocompatibility and the anion-exchange properties of LDHs, they have been widely employed as support matrices of anionic drugs in DDS systems, among others. However, LDH is very sensitive to acid environments and the drug is often completely released in the stomach media (pH=1.2). Thus, the preparation of core-shell LDH-drug hybrids coated with a protective polymeric matrix, has been recently proposed to preserve the release properties through the gastrointestinal tract [44].
Khan, A. I., et al. (2001), reported that, a series of pharmaceutically active compounds including diclofenac, gemfibrozil, ibuprofen, naproxen, 2-propylpentanoic acid, 4-biphenylacetic acid and tolfenamic acid can be reversibly intercalated into a LDHs, initial studies suggest that these materials may have application as the basis of a novel tune able DDS.
Fig. 4, shows release profile plots for the deintercalation of diclofenac and of gemfibrozil on the addition of phosphate buffer at pH=4 and pH=7. At pH=4 the measured release of diclofenac and gemfibrozil is very fast with almost full deintercalation observed in less than 10 min. Surprisingly, the release curve for gemfibrozil at pH=7 is almost identical to the profile recorded at pH=4. At pH=7 the release of diclofenac is much slower and only after 28 min is 90% of the drug released into solution [45].
Li, B., et al. (2004) reported that the anti-inflammatory drug fenbufen has been intercalated into LDHs for the first time by co-precipitation under a nitrogen atmosphere. Drug release characteristics of the pillared LDH materials were investigated by a dissolution test in a simulated intestinal fluid (buffer at pH=7.8). The results show that the drug release of supramolecular LDH materials was a slow process, especially in the case of Mg/Al intercalated materials, suggesting that these drugs-inorganic hybrid materials can be used as an effective DDS [46].
Tamura et al. (2004) studied the intercalation of adenosine triphosphate (ATP) into MgAl LDH as a model for a DDS. Two intercalation methods were used: ion-exchange using nitrate as the interlayer anion and co-precipitation, adding Mg2+ and Al3+ ions into a sodium hydroxide solution. The stability diagram for aluminum hydroxide shows that it starts to form even at pH=4.0 (Fig. 5) and can contaminate the hydrotalcite that forms at higher pH (8.0 and 10). Pure hydrotalcite is not obtained with method B. From these results it was concluded that method A with a pH=10 and with an aging time of 24 h provides well crystallized pure hydrotalcite with a large ion-exchange capacity [47].
Three representative nonsteroidal anti-inflammatory drug molecules, Ibuprofen, Diclofenac, and Indomethacin, have been intercalated within the galleries of an anionic clay, Mg-Al LDHs (LDH) [48].
Gordijo et al. (2005) reported the immobilization of ibuprofen and copper-ibuprofen drugs on LDHs. Ibuprofen was intercalated in LDHs by: ion-exchange, reconstruction and co-precipitation. The drug and the copper-ibuprofen were also immobilized by adsorption on the external LDH surfaces. Pharmacological interests were compared considering the amounts of immobilized drugs and, most of all, their buffering properties. Samples obtained by exchange and co-precipitation exhibited poor buffering property, but contained high amounts of drug. Adsorption samples despite their buffering property contained low amounts of ibuprofen. The reconstructed hybrid systems combined significant amounts of immobilized drug with good buffering property. These organic–inorganic materials based on LDHs may be an interesting new formulation aiming to decrease gastric irritation, mainly due to their buffering property [49].
Controlled release formulation of an herbicide, 2,4-dichlorophenoxyacetate (24D) was developed by the virtue of the formation of organic-inorganic nanohybrid material and its ion-exchange property developed by bin Hussein, M. Z., et al. (2005). The inorganic Zn-Al LDHs (ZAL) was used as a matrix, hosting an active agent or a guest, 24D by self-assembly technique [50].
Concerning the interaction between antibiotics and LDH, there are some emphasized works. Mohanambe and Vasudevan (2005) have intercalated carboxymethyl beta-cyclodextrin cavities within the galleries of Mg-Al layered double hydroxide. The cyclodextrin functionalized LDH adsorbed neutral and nonpolar guest molecules [48].
Oh, J. M., et al. (2006), have been successful to intercalate anticancer drug, methotrexate (MTX), into LDHs, Mg2Al(OH)6(NO3)·0.1 H2O, through conventional co-precipitation method. LDHs are endowed with great potential for delivery vector, since their cationic layers lead to safe reservation of bio functional molecules such as drug molecules or genes, and their ion-exchangeability and solubility in acidic media (pH<4) give rise to the controlled release of drug molecules. Moreover, it has been partly confirmed that LDH itself is non-toxic and facilitate the cellular permeation [51].
Nanostructural drug-inorganic clay composite involving a pharmaceutically active compound captopril (Cpl) intercalated Mg-Al-LDHs (Cpl-LDHs) with Mg/Al molar ratio of 2.06 has been assembled by co-precipitation method. Zhang, H., et al. (2006) considered that the dissolution mechanism is mainly responsible for the release behavior of Cpl-LDHs at pH=4.60, while the ion-exchange one is responsible for that at pH=7.45 [29].
Magnesium-aluminum-chloride-LDHs (MgAl-Cl-LDHs) intercalated with low molecular weight heparin (LMWH) were prepared for the first time by the co-precipitation method by Gu, Z, et al. (2008). In vitro release tests of LMWH-LDH in pH=7.4 PBS at 37 ̊C show a biphasic and sustained profile of LMWH anion release with ~20% in the first 12 h and another ~20% in the following 108 h. [52].
The morphology of individual nanohybrid particles is further examined using TEM (Fig. 6). As a consequence of LMWH intercalation the LDH nanoparticle shape changes from regular hexagon to ellipse (images a and b in Fig. 6). At higher magnification (images c and d in Fig. 6), the layered structure of both Cl-LDH and LMWH20-LDH is clearly observed. The dark and bright stripes represent the mixed hydroxide layers and the interlayers with exchangeable organic (LMWHn-) and inorganic (Cl-, CO32-) anions, respectively. The average (003) spacing was calculated by measuring 10 repeated layer-interlayer units in 5 visual fields (images c and d in Fig. 6).
As shown in Fig. 6c, the pristine Cl-LDH has an average (003) spacing of ~0.65 nm, in line with the spacing determined using XRD (0.77 nm). The layered structure of LDH is still preserved after the incorporation of LMWH anions to form LMWH20-LDH (Fig. 6d). The average (003) spacing of LMWH20-LDH is ~1.00 nm, between 0.77 nm (Cl-LDH) and 1.40 nm (LMWH100-LDH) calculated from XRD data, and thus corresponding to partial intercalation [52].
The Enalaprilate (Enal), an active pharmaceutical component, was intercalated into LDHs (MgAl-LDH) by an ion-exchange reaction and it was carried out by Ribeiro, C., et al. (2009). The resulting hybrid system containing HDL-Enal-XG(3) slowly released the Enal. In an 8 h of test, the system protected 40% (w/v) of the drug [53].
In the other research which was performed by Li, F., et al. (2009), some nonsteroidal anti-inflammatory drugs (Indomethacin) were chosen as models of poorly water-soluble drugs. They were intercalated in MgAl-LDH and solubility measurements in acidic medium were performed. In acid pH hydrotalcite quickly dissolves and releasing the drug in molecular form [54].
Ibuprofen (IBU) has been chosen as a model drug, being intercalated in a Mg-Al LDH matrix by Aranda, P., et al. (2010). The combination of alginate and zein biopolymers gives rise to new matrices for DDS that can be used for direct encapsulation of a drug (e.g. IBU) and also to develop bio nanocomposite materials with drug-intercalated LDH systems. [44].
Qin, L., et al. (2010) intercalated anti-tumor drug Podophyllotoxin (PPT) into LDHs and investigated the in vitro cytotoxicity to tumor cells, the cellular uptake and in vivo anti-tumor inhibition of PPT-LDH [55].
Hydrophobic anticancer drug 5-fluorouracil (5-FU) has been included in the carboxymethyl modified β-cyclodextrin (CMCD), and the inclusion complex (5-FU/CMCD) was further intercalated into galleries of zinc aluminum LDHs (ZnAl-LDH) by the ion-exchange method by Jin, L., et al. (2010). It was found that 5-FU was released faster in pH=7.2 than in the acidic mediums (pH=4.8), and the released amount was higher [56].
The purpose of this study was to investigate the use of nanoparticulates composed of LDHs clays to bind various antibiotics (tetracycline, doxorubicin (DOX), 5-fluorouracil, vancomycin (VAN), sodium fusidate (SF)) and release them in a controlled manner (Chakraborti, M., et al. (2012)). MgAl (carbonate) LDHs clays may be useful for controlling release applications at sites requiring long-term antibiotic exposure as they maintain the drug in a non-degraded state and release effective amounts of drug over long time periods [57].
In the other study, which was carried out by Saifullah, B., et al. (2013) para-amino salicylic acid (PASA) was intercalated into zinc/aluminum-LDHs (ZLDHs) by two methods, direct and indirect, to form nanocomposites: PASA nanocomposite prepared by a direct method (PASA-D) and PASA nanocomposite prepared by an indirect method (PASA-I). The in vitro release properties of the drug were investigated in physiological simulated phosphate-buffered saline solution of pH=7.4 and 4.8 [58].
Magnesium-aluminum LDHs intercalated with antitumor drug etoposide (VP16) were prepared for the first time using a two-step procedure, developed by Qin, L., et al. (2013). The mechanism of VP16-LDH release in the phosphate buffered saline solution at pH=7.4 is likely controlled by the diffusion of VP16 anions from inside to the surface of LDH particles [59].
In this research Li, L., et al. (2014), employed LDHs to simultaneously deliver an anticancer drug 5-fluorouracil (5-FU) and all stars cell death siRNA (CD-siRNA) for effective cancer treatment. The strategy takes advantage of the LDH anion-exchange capacity to intercalate 5-FU into its interlayer spacing and load siRNA on the surface of LDH nanoparticles. The combination of CD-siRNA and anticancer drug 5-FU with the same LDH particles significantly enhanced cytotoxicity to three cancer cell lines, e.g. MCF-7, U2OS and HCT-116, compared to the single treatment with either CD-siRNA or 5-FU. This enhancement is probably a result of coordinate mitochondrial damage process. Thus, the strategy to co-deliver siRNA and an anticancer drug by LDHs has great potential to overcome the drug resistance and enhance cancer treatment [60].
As an alternative to degradable organic coatings the possibility of using LDHs to generate implant coatings for controlled drug delivery was evaluated in vivo and in vitro. Coatings prepared from LDH suspensions dissolved slowly and appeared compatible with cultured cells. LDH coatings loaded with an antibiotic resulted in antibacterial effects in vitro. The LDH coating prolonged the drug release period and improved the proliferation of adherent cells in comparison to pure drug coatings. However, during incubation in physiological solutions the LDH coatings became brittle and pieces occasionally detached from the surface. For stress protection porous titanium implants were investigated as a substrate for the coatings. The pores prevented premature detachment of the coatings.
The other work that was reported by Barkhordari, S., et al. (2014), deals with the preparation of new DDSs based on the combination of LDHs and a pH-sensitive polymer, carboxymethyl cellulose (CMC). Ibuprofen (IBU) has been chosen as a model drug, being intercalated between LDH layers in order to prepare LDH-IBU nanohybrids (Fig. 7). The LDH-IBU nanohybrids and CMC/LDH-IBU nanocomposite beads were tested for controlling release of ibuprofen under conditions simulating the gastrointestinal tract, pH=1.2 (stomach) and 7.4 (intestinal tract). Studies of ibuprofen release from LDH-IBU nanohybrids and CMC/LDH-IBU nanocomposite beads show a better protection against drug release for a CMC/LDH-IBU nanocomposite at the stomach pH and a controlled release in the intestinal tract conditions [61].
In this work, (Rojas, R., et al. (2015)) these aspects are studied using LDHs intercalated with ibuprofen (Ibu), naproxen (Nap) or ketoprofen (Ket) to understand the behavior of intercalation compounds as drug carriers.
The particle size and shape of LDH-D was assessed by SEM images. The SEM images showed the morphology of LDH particles. LDH particles were formed by agglomeration of smaller units or platelets of around 300 nm (Fig. 8). These platelets presented high diameter to thickness ratio and irregular shape [62].
In the other study, which was done by Mondal, S., et al. (2016), the efficacy of Mg1‐xAlx (NO3)x.(OH)2 LDH nanoparticles as a carrier and for controlled release of one of the non-Steroidal anti-inflammatory drugs (NSAID), sodium salicylate. The cumulative release kinetic of salicylate from MgAl-LDH-SA hybrids in phosphate buffer saline (PBS) at pH=7.4 showed a sustained release of salicylate up to 72 h that closely resembled first order release kinetics through a combination of drug diffusion and dissolution of LDH under physiological conditions (Fig. 9) [63].
Hydrophobic anticancer drug, raloxifene hydrochloride (RH) is intercalated into a series of magnesium aluminum LDHs with various charge density anions through ion-exchange technique for controlled drug delivery by Senapati, S., et al. (2016). The particle nature of the LDH in presence of drug is determined through electron microscopy and surface morphology. The release of drug from the RH intercalated LDHs was made very fast or sustained by altering the exchangeable anions followed by the modified Freundlich and parabolic diffusion models. The drug release rate is explained from the interactions between the drug and LDHs along with order–disorder structure of drug intercalated LDHs. Nitrate bound LDH exhibits greater interaction with drug and sustained drug delivery against the loosely interacted phosphate bound LDH-drug, which shows fast release. Cell viability through MTT assay suggests drug intercalated LDHs as better drug delivery vehicle for cancer cell line against the poor bioavailability of the pure drug (Fig. 10) [64].
A novel MgAl-LDH nanoparticle/thermogel composite DDS for sustained release of Brimonidine (Bri) has been designed, prepared, and characterized by Sun, J., et al. (2017), for treatment of severe glaucoma. The in vitro drug release of Bri@LDH/Thermogel shows a sustainable release for up to 144 h, a significant delay of drug release compared to that from Bri@LDH nanoparticles. [65].
This study, which was reported by (Wu, J., et al. (2017)) focuses on the synthesis and in vitro evaluation of magnetic nanocomposites (Fe3O4@LDH) as methotrexate (MTX) delivery system for targeted anticancer therapy and 84.94% MTX was released within 48 h, at pH=3.5 via the co-effect of dissolution of LDH layer and ion-exchange [66].
The 2D mono LDHs (MLDH) nanosheets were employed by Mei, X., et al. (2018) to localize doxorubicin (DOX), an anticancer drug, with a loading capacity of as high as 3.6 mg mg–1 (w/w). With the assistance of the targeting agent folic acid (FA), DOX-FA/MLDHs demonstrate targeted cellular uptake and superior anticancer behavior based on in vitro tests performed with cancer cells [5].
The pH-responsive smart capsules were developed by Katagiri, K., et al. (2018), the layer-by-layer assembly with a colloid templating technique. Acid-soluble inorganic nanosheets were prepared from MgAl-LDH by an exfoliation technique [67].
The intercalation of Kynurenic acid (KYNA) molecules into biocompatible MgAl-LDH lamellae were investigated by Deák, Á., et al. (2018). LDH layers were almost completely dissolved at gastric pH during the in vitro study and the anti-ulcerant KYNA molecules were released from the destroyed interlayers. The release properties of KYNA were studied at the pH of human saliva at a value of 6.70 and at pH of SGF (pH=1.5), as well. The release study of the KYNA/LDH has also been performed at pH=1.5. Fig. 11, presents the drug release profiles, which were carried out over a period of 240 min and at body temperature (37 °C) and in physiological saline. The released concentration of the drug was determined spectrophotometrically. The solubility and thus the release rate of anionic KYNA depend on pH [68].
In the other work, Allou, N., et al. (2018). Hybrid materials containing citric acid cross-linked carboxymethyl cellulose (CMC) and norfloxacin (NOR) intercalated layered double hydroxide (LDH) deposited over the surface of functionalized carbon (AC) were prepared. The synthesized CMC@AC-LDHNOR nanohybrids were characterized using different techniques and in vitro NOR release behaviors were investigated in phosphate buffer saline, pH=7.4 at 37 °C [69].
In this work, Komarala, E. P., et al. (2018), were reported the loading of cefotaxime sodium on MgAl layered double hydroxide (Cefo-LDH) and the formation of a nanohybrid with a fenugreek polymer (CLF nanohybrid). This nanohybrid was synthesized through the method of anion-exchange followed by sonication. The as-synthesized CLF nanohybrid was thoroughly characterized by XRD, FT-IR and zeta potential measurements, which revealed that the cefotaxime drug was bound to the LDH surface. The drug loading capacities of Cefo-LDH and the CLF nanohybrid were found to be 85.6 and 72.5 μg mg−1, respectively. The drug released from the CLF nanohybrid demonstrates a controlled and sustained profile at pH=7.3 over a period of 72 h [70].
In this article, Capsoni, D., et al. (2018), synthesize by co-precipitation method the hybrid compound Carprofen-Zn2Al-LDH. Carprofen, a poorly soluble anti-inflammatory drug, could also benefit of the association with a natural antacid such as LDH, to reduce the gastric irritation after its administration. The dissolution tests clearly demonstrate a significant improvement of the drug release rate when carprofen is in the form of hybrid compound [71].
The potential of the layered gadolinium hydroxide (LGdH) [Gd2(OH)5]Cl.yH2O (LGdH-Cl) for simultaneous drug delivery and magnetic resonance imaging was explored by Xu, Y., et al. (2018), in this work. Three non-steroidal anti-inflammatory drugs (diclofenac [dic], ibuprofen [ibu], and naproxen [nap]) were intercalated into LGdH-Cl for the first time, using three different routes (ion-exchange intercalation, co-precipitation, and exfoliation-self-assembly). The materials prepared by co-precipitation in general have noticeably higher drug loadings than those produced by ion-exchange or self-assembly, as a result of the incorporation of some neutral drug into the composites. The LGdH-drug intercalates are stable at neutral pH, but rapidly degrade in acidic conditions to free Gd3+ into solution. While LGdH-nap releases its drug loading into solution very rapidly (within ca. 1.5 h) at pH=7.4, LGdH-dic show sustained release over 4 h, and LGdH-ibu extends this to 24 h. The biocompatibility of selected LGdH-drug composites was assessed using in vitro cell viability studies. The results of performing these with the solid LGdH materials are presented in Fig. 12. At concentrations of 526 μg mL-1, both LGdH-Cl and LGdH-ibu are highly biocompatible, and in fact appear to encourage cell growth. In contract, LGdH-dic causes some cell death, with a mean viability of 71 %. At a lower concentration of 270 μg mL-1 all three LGdH materials explored have very good biocompatibility, resulting in cell counts higher than the untreated control cells. Further experiments were undertaken with solutions made from LGdH suspensions (Fig. 12). In all cases here the cell viability was indistinguishable from the untreated cells, thereby confirming the biocompatibility of the LGdH-drug materials. [72].
The clinic application of magnesium is mainly impeded by its poor corrosion resistance and implants with localized drug delivery attract tremendous interest (Peng, F., et al. (2018)). Here, Mg/Al layered double hydroxide (Mg-Al LDH) film was in situ prepared on AZ31 alloy by a hydrothermal process, and further calcined to form metastable mixed oxides, also named Mg/Al layered double oxide (LDO). Finally, immersing in 5-Fluorouracil (5-FU) solution, Mg/Al LDO would revert to Mg/Al LDH via a memory effect, and be loaded with 5-FU (#LDO-5FU). This work broadens the application of calcined LDH and provides a new strategy in the field of surface modification of magnesium alloy [73].
The use of clays in various fields is well known and familiar to mankind, contributing to human health and life. In addition to their traditional applications, many types of clays, clay minerals, but also LDHs have been recently applied to diverse commercial products as simple adding or adjuvants. Increasing attention has been recently given to advanced applications, in particular based on new interdisciplinary fields developed for protective and controlled delivery of various functional compounds. The promising potential of clay minerals and LDHs offers novel perspectives for inorganic-biomaterial hybrids, and practical applications as new delivery systems are not so far. LDHs can be used in a wide range of applications in health. LDHs are being used as excipients and active principles in the pharmaceutical industry. Development of new pharmaceutical formulations is observed, based on LDHs, for cancer therapy.
The authors declare that there is no conflict of interests regarding the publication of this manuscript.
[1] K. Ladewig, Z.P. Xu, G.Q. Lu, Layered double hydroxide nanoparticles in gene and drug delivery, Expert. Opin. Drug. Del., 6, 907(2009).
[2] S.-J. Choi, J.-H. Choy, Layered double hydroxide nanoparticles as target-specific delivery carriers: uptake mechanism and toxicity, Nanomedicine, 6, 803(2011).
[3] G.-F. Xiao, H.-Y. Zeng, Q.-J. Huang, W. Zhang, J.Z. Du, H. Duan, C. Chen, Facile Preparation of Modifying Layered Double Hydroxide Nanoparticles for Drug Delivery, J. Nanosci. Nanotechnol, 18, 5256(2018).
[4] G. Huang, K.-L. Zhang, S. Chen, S.-H. Li, L.-L. Wang, L.-P. Wang, R. Liu, J. Gao, H.-H. Yang, Manganese-iron layered double hydroxide: a theranostic nanoplatform with pH-responsive MRI contrast enhancement and drug release, J. Mater. Chem. B, 5, 3629(2017).
[5] X. Mei, S. Xu, T. Hu, L. Peng, R. Gao, R. Liang, M. Wei, D.G. Evans, X. Duan, Layered double hydroxide monolayers for controlled loading and targeted delivery of anticancer drugs, Nano. Res, 11, 195(2018).
[6] S.P. Newman, W. Jones, Synthesis, characterization and applications of layered double hydroxides containing organic guests, New J. Chem., 22, 105(1998).
[7] D.P. Debecker, K. Bouchmella, C. Poleunis, P. Eloy, P. Bertrand, E.M. Gaigneaux, P.H. Mutin, Design of SiO2−Al2O3−MoO3 metathesis catalysts by nonhydrolytic sol-gel, Chem. Mater., 21, 2817(2009).
[8] G. Pshinko, A. Kosorukov, L. Puzyrnaya, V. Goncharuk, Layered double hydroxides intercalated with EDTA as effective sorbents for U (VI) recovery from wastewater, Radiochem., 53, 303(2011).
[9] M.I. Carretero, M. Pozo, Clay and non-clay minerals in the pharmaceutical industry: Part I. Excipients and medical applications, Appl. Clay Sci., 46, 73(2009).
[10] P.B. Panici, S. Basile, F. Maneschi, A.A. Lissoni, M. Signorelli, G. Scambia, R. Angioli, S. Tateo, G. Mangili, D. Katsaros, Systematic pelvic lymphadenectomy vs no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial, JNCI: J. Natl. Cancer. Inst., 100, 1707(2008).
[11] V. Rives, M. del Arco, C. Martín, Intercalation of drugs in layered double hydroxides and their controlled release: A review, Appl. clay sci., 88, 239(2014).
[12] V. Ambrogi, L. Perioli, C. Pagano, F. Marmottini, M. Ricci, A. Sagnella, C. Rossi, Use of SBA-15 for furosemide oral delivery enhancement, Eur. J. Pharm. Sci., 46, 43(2012).
[13] E. Conterosito, G. Croce, L. Palin, C. Pagano, L. Perioli, D. Viterbo, E. Boccaleri, G. Paul, M. Milanesio, Structural characterization and thermal and chemical stability of bioactive molecule–hydrotalcite (LDH) nanocomposites, Phys. Chem. Chem. Phys., 15, 13418(2013).
[14] L. Perioli, C. Pagano, Inorganic-organic hybrids to improve the performances of anti-inflammatory topical formulations, Int. J., 5 (2016).
[15] S. Lee, C.Y. Heo, Corporate social responsibility and customer satisfaction among US publicly traded hotels and restaurants, Int. J. Hosp. Manag., 28, 635 (2009).
[16] M. Shamsayei, Y. Yamini, H. Asiabi, M. Safari, On-line packed magnetic in-tube solid phase microextraction of acidic drugs such as naproxen and indomethacin by using Fe3O4@SiO2@layered double hydroxide nanoparticles with high anion exchange capacity, Microchim. Acta, 185, 192 (2018).
[17] C. You, Y. Ji, Z. Liu, X. Xiong, X. Sun, Ultrathin CoFe-Borate Layer Coated CoFe-Layered Double Hydroxide Nanosheets Array: A Non-Noble-Metal 3D Catalyst Electrode for Efficient and Durable Water Oxidation in Potassium Borate, ACS Sustain. Chem. Eng., 6, 1527(2018).
[18] N. Chen, C. Long, Y. Li, D. Wang, H. Zhu, High-performance layered double hydroxide/poly (2, 6-dimethyl-1, 4-phenylene oxide) membrane with porous sandwich structure for anion exchange membrane fuel cell applications, J. Membrane Sci., 552, 51(2018).
[19] J. Yu, Q. Wang, D. O'Hare, L. Sun, Preparation of two dimensional layered double hydroxide nanosheets and their applications, Chem. Soc. Rev., 46, 5950(2017).
[20] A.U. Kura, M.Z. Hussein, S. Fakurazi, P. Arulselvan, Layered double hydroxide nanocomposite for drug delivery systems; bio-distribution, toxicity and drug activity enhancement, Chem. Cent. J., 8, 47(2014).
[21] G. Chen, I. Roy, C. Yang, P.N. Prasad, Nanochemistry and nanomedicine for nanoparticle-based diagnostics and therapy, Chem. Rev, 116, 2826(2016).
[22] S. Mondal, S. Dasgupta, K. Maji, MgAl-layered double hydroxide nanoparticles for controlled release of salicylate, Mater. Sci. Eng. C, 68, 557(2016).
[23] H. Heinz, C. Pramanik, O. Heinz, Y. Ding, R.K. Mishra, D. Marchon, R.J. Flatt, I. Estrela-Lopis, J. Llop, S. Moya, Nanoparticle decoration with surfactants: molecular interactions, assembly, and applications, Surf. Sci. Rep., 72, 1 (2017).
[24] C. Forano, F. Bruna, C. Mousty, V. Prevot, Interactions Between Biological Cells and Layered Double Hydroxides: Towards Functional Materials, Chem. Rec, (2018).
[25] R.K. Kankala, Y. Kuthati, C.-L. Liu, C.-H. Lee, Hierarchical coated metal hydroxide nanoconstructs as potential controlled release carriers of photosensitizer for skin melanoma, RSC Adv., 5, 42666(2015).
[26] L. Qiu, Y. Gao, P. Lu, D. O'hare, Q. Wang, Synthesis and properties of polypropylene/layered double hydroxide nanocomposites with different LDHs particle sizes, J. Appl. Polym. Sci., 135, 46204(2018).
[27] X. Tao, D. Liu, W. Cong, L. Huang, Controllable synthesis of starch-modified ZnMgAl-LDHs for adsorption property improvement, Appl. Surf. Sci., (2018).
[28] H.N. Tran, C.-C. Lin, H.-P. Chao, Amino acids-intercalated Mg/Al layered double hydroxides as dual-electronic adsorbent for effective removal of cationic and oxyanionic metal ions, Sep. Purif. Technol., 192, 36(2018).
[29] H. Zhang, K. Zou, S. Guo, X. Duan, Nanostructural drug-inorganic clay composites: Structure, thermal property and in vitro release of captopril-intercalated Mg-Al-layered double hydroxides, J. Solid State Chem., 179, 1792(2006).
[30] Z. Gu, J.J. Atherton, Z.P. Xu, Hierarchical layered double hydroxide nanocomposites: structure, synthesis and applications, Chem. Comm., 51, 3024(2015).
[31] J. Wang, R. Zhu, B. Gao, B. Wu, K. Li, X. Sun, H. Liu, S. Wang, The enhanced immune response of hepatitis B virus DNA vaccine using SiO2@LDH nanoparticles as an adjuvant, Biomaterials, 35, 466(2014).
[32] S. Wu, K. Hui, K. Hui, One-dimensional core-shell architecture composed of silver nanowire@ hierarchical nickel-aluminum layered double hydroxide nanosheet as advanced electrode materials for pseudocapacitor, J. Phys. Chem. C, 119, 23358(2015).
[33] R. Soltani, A. Shahvar, M. Dinari, M. Saraji, Environmentally-friendly and ultrasonic-assisted preparation of two-dimensional ultrathin Ni/Co-NO3 layered double hydroxide nanosheet for micro solid-phase extraction of phenolic acids from fruit juices, Ultrason. sonochem., 40, 395(2018).
[34] L. Dang, H. Liang, J. Zhuo, B.K. Lamb, H. Sheng, Y. Yang, S. Jin, Direct Synthesis and Anion Exchange of Non-Carbonate-Intercalated NiFe Layered Double Hydroxides and the Influence on Electrocatalysis, Chem. Mater., (2018).
[35] L. Valdés, I. Pérez, L.C. De Ménorval, E. Altshuler, J.O. Fossum, A. Rivera, A simple way for targeted delivery of an antibiotic: In vitro evaluation of a nanoclay-based composite, PloS one, 12, e0187879 (2017).
[36] D. Cao, Z. Xu, Y. Chen, Q. Ke, C. Zhang, Y. Guo, Ag‐loaded MgSrFe‐layered double hydroxide/chitosan composite scaffold with enhanced osteogenic and antibacterial property for bone engineering tissue, J. Biomed. Mater. Res. B Appl. Biomate., 106, 863(2018).
[37] M. Richetta, P. Medaglia, A. Mattoccia, A. Varone, R. Pizzoferrato, Layered Double Hydroxides: Tailoring Interlamellar Nanospace for a Vast Field of Applications, J. Mater. Sci. Eng., 6, 2169(2017).
[38] D.G. Evans, X. Duan, Preparation of layered double hydroxides and their applications as additives in polymers, as precursors to magnetic materials and in biology and medicine, Chem. Comm., 485(2006).
[39] S.-Y. Kwak, Y.-J. Jeong, J.-S. Park, J.-H. Choy, Bio-LDH nanohybrid for gene therapy, Solid State Ionics, 151, 229(2002).
[40] C.F. Bennett, M.-Y. Chiang, H. Chan, J. Shoemaker, C.K. Mirabelli, Cationic lipids enhance cellular uptake and activity of phosphorothioate antisense oligonucleotides, Mol. Pharmacol., 41, 1023(1992).
[41] J.-M. Oh, D.-H. Park, S.-J. Choi, J.-H. Choy, LDH nanocontainers as bio-reservoirs and drug delivery carriers, Recent pat. nanotech., 6, 200(2012).
[42] S.-M. Lee, S.T. Nguyen, Smart nanoscale drug delivery platforms from stimuli-responsive polymers and liposomes, Macromolecules, 46, 9169(2013).
[43] G. Mishra, B. Dash, S. Pandey, Layered double hydroxides: A brief review from fundamentals to application as evolving biomaterials, Appl. Clay Sci., 153, 172(2018).
[44] P. Aranda, M. Darder, E. Ruiz-Hitzky, Bionanocomposites based on alginate–zein/layered double hydroxide materials as drug delivery systems, J. Mater. Chem., 20, 9495(2010).
[45] A.I. Khan, L. Lei, A.J. Norquist, D. O'Hare, Intercalation and controlled release of pharmaceutically active compounds from a layered double hydroxideElectronic supplementary information (ESI) available: Fig. S1: X-ray diffraction patterns of (a)[LiAl2(OH)6]Cl·H2O and (b) LDH/Ibuprofen intercalate. Chem. Comm., 2342(2001).
[46] B. Li, J. He, D. G. Evans, X. Duan, Inorganic layered double hydroxides as a drug delivery system—intercalation and in vitro release of fenbufen, Appl. Clay Sci., 27, 199(2004).
[47] H. Tamura, J. Chiba, M. Ito, T. Takeda, S. Kikkawa, Synthesis and characterization of hydrotalcite-ATP intercalates, Solid State Ionics, 172, 607(2004).
[48] L. Mohanambe, S. Vasudevan, Anionic clays containing anti-inflammatory drug molecules: Comparison of molecular dynamics simulation and measurements, J. Phys. Chem. B, 109, 15651(2005).
[49] C.R. Gordijo, C.A. Barbosa, A.M.D.C. Ferreira, V.R. Constantino, D. de Oliveira Silva, Immobilization of ibuprofen and copper-ibuprofen drugs on layered double hydroxides, J. pharm. sci., 94, 1135(2005).
[50] M.Z. bin Hussein, A.H. Yahaya, Z. Zainal, L.H. Kian, Nanocomposite-based controlled release formulation of an herbicide, 2, 4-dichlorophenoxyacetate incapsulated in zinc-aluminium-layered double hydroxide, Sci. Tech. Adv. Mater., 6, 956(2005).
[51] J.-M. Oh, M. Park, S.-T. Kim, J.-Y. Jung, Y.-G. Kang, J.-H. Choy, Efficient delivery of anticancer drug MTX through MTX-LDH nanohybrid system, J. Phys. Chem. Solids, 67, 1024(2006).
[52] Z. Gu, A.C. Thomas, Z.P. Xu, J.H. Campbell, G.Q. Lu, In vitro sustained release of LMWH from MgAl-layered double hydroxide nanohybrids, Chem. Mater., 20, 3715(2008).
[53] C. Ribeiro, G.G.C. Arizaga, F. Wypych, M.R. Sierakowski, Nanocomposites coated with xyloglucan for drug delivery: In vitro studies, Int. J. Pharm., 367, 204(2009).
[54] F. Li, L. Jin, J. Han, M. Wei, C. Li, Synthesis and controlled release properties of prednisone intercalated Mg-Al layered double hydroxide composite, Ind. Eng. Chem. Res., 48, 5590(2009).
[55] L. Qin, M. Xue, W. Wang, R. Zhu, S. Wang, J. Sun, R. Zhang, X. Sun, The in vitro and in vivo anti-tumor effect of layered double hydroxides nanoparticles as delivery for podophyllotoxin, Int. J. Pharm., 388, 223(2010).
[56] L. Jin, Q. Liu, Z. Sun, X. Ni, M. Wei, Preparation of 5-fluorouracil/β-cyclodextrin complex intercalated in layered double hydroxide and the controlled drug release properties, Ind. Eng. Chem. Res., 49, 11176(2010).
[57] M. Chakraborti, J.K. Jackson, D. Plackett, S.E. Gilchrist, H.M. Burt, The application of layered double hydroxide clay (LDH)-poly (lactide-co-glycolic acid)(PLGA) film composites for the controlled release of antibiotics, J. Mater. Sci. Mater. Med., 23, 1705(2012).
[58] B. Saifullah, M.Z. Hussein, S.H. Hussein-Al-Ali, P. Arulselvan, S. Fakurazi, Antituberculosis nanodelivery system with controlled-release properties based on para-amino salicylate–zinc aluminum-layered double-hydroxide nanocomposites, Drug Des. Dev. Ther., 7, 1365(2013).
[59] L. Qin, M. Wang, R. Zhu, S. You, P. Zhou, S. Wang, The in vitro sustained release profile and antitumor effect of etoposide-layered double hydroxide nanohybrids, Int. J. Nanomed., 8, 2053(2013).
[60] L. Li, W. Gu, J. Chen, W. Chen, Z.P. Xu, Co-delivery of siRNAs and anti-cancer drugs using layered double hydroxide nanoparticles, Biomaterials, 35, 3331(2014).
[61] S. Barkhordari, M. Yadollahi, H. Namazi, pH sensitive nanocomposite hydrogel beads based on carboxymethyl cellulose/layered double hydroxide as drug delivery systems, J. Polym. Res., 21, 454(2014).
[62] R. Rojas, Y.G. Linck, S.L. Cuffini, G.A. Monti, C.E. Giacomelli, Structural and physicochemical aspects of drug release from layered double hydroxides and layered hydroxide salts, Appl. Clay Sci., 109 119(2015).
[63] S. Mondal, S. Dasgupta, K. Maji, MgAl-Layered Double Hydroxide Nanoparticles for controlled release of Salicylate, Mater. Sci. Eng. C., 68 557(2016).
[64] S. Senapati, R. Thakur, S.P. Verma, S. Duggal, D.P. Mishra, P. Das, T. Shripathi, M. Kumar, D. Rana, P. Maiti, Layered double hydroxides as effective carrier for anticancer drugs and tailoring of release rate through interlayer anions, J. Control. Release, 224, 186(2016).
[65] J. Sun, Y. Lei, Z. Dai, X. Liu, T. Huang, J. Wu, Z.P. Xu, X. Sun, Sustained release of brimonidine from a new composite drug delivery system for treatment of glaucoma, ACS appl. mater. interfaces, 9, 7990(2017).
[66] J. Wu, A. Deng, W. Jiang, R. Tian, Y. Shen, Synthesis and in vitro evaluation of pH-sensitive magnetic nanocomposites as methotrexate delivery system for targeted cancer therapy, Mater. Sci. Eng. C., 71, 132 (2017).
[67] K. Katagiri, Y. Shishijima, K. Koumoto, K. Inumaru, Preparation of pH-Responsive hollow capsules via layer-by-layer assembly of exfoliated layered double hydroxide nanosheets and polyelectrolytes, J. Nanosci. Nanotechnol, 18, 110(2018).
[68] Á. Deák, E. Csapó, Á. Juhász, I. Dékány, L. Janovák, Anti-ulcerant kynurenic acid molecules intercalated Mg/Al-layered double hydroxide and its release study, Appl. Clay Sci., 156 (2018) 28-35.
[69] N. Allou, A. Yadav, M. Pal, R.L. Goswamee, Biocompatible nanocomposite of carboxymethyl cellulose and functionalized carbon-norfloxacin intercalated layered double hydroxides, Carbohyd. polym., 186, 282(2018).
[70] E.P. Komarala, S. Doshi, S. Thiyagarajan, M. Aslam, D. Bahadur, Studies on drug release kinetics and antibacterial activity against drug-resistant bacteria of cefotaxime sodium loaded layered double hydroxide–fenugreek nanohybrid, New J. Chem., 42, 129 (2018).
[71] D. Capsoni, I. Quinzeni, G. Bruni, V. Friuli, L. Maggi, M. Bini, Improving the Carprofen Solubility: Synthesis of the Zn2Al-LDH Hybrid Compound, J. Pharm. Sci., 107, 267(2018).
[72] Y. Xu, A. Goyanes, Y. Wang, A. Weston, P.-W. So, C. Geraldes, A. Fogg, A. Basit, G.R. Williams, Layered gadolinium hydroxides for simultaneous drug delivery and imaging, Dalton Trans., (2018).
[73] F. Peng, D. Wang, H. Cao, X. Liu, Loading 5-Fluorouracil into calcined Mg/Al layered double hydroxide on AZ31 via memory effect, Mater. Lett., 213, 383(2018).

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Server address: server.convoytrucking.netYou can download SA-MP 0.3.7 here: http://www.sa-mp.com/download.php
Quote from: Rahail on December 14, 2013, 03:00[video]I motion of the other trucks needs fixed so there smooth and not all glitchy :O
Did anybody here play pre-0.3 SAMP? There was a huge desyncing issues and lag. That is pre-Alpha while Alpha is really really early test version. Thats even earlier and buggier test version than the early test version
Can you post the link, the video does not work for me here...
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Clericer posted a topic in MySQL HelpHey guys, this is my first post, so please tell me if i do something wrong. My Problem: I'm using mysql innodb on Ubunut 18.04 > sql Ver 14.14 Distrib 5.7.27 < and im running unto some strange issues. First: if i change the values in my.cnf for innodb_buffer_pool_size=48G mysql using 50gb of ram but the database is 11gb large (there is only one Database) . Can someone tell me what mysql is doing? where are the 37gb of data comming from? I have some heavy select and write querys and i need fast results. At the beginning with my mysql experiences i wanted to create a fstab ram directory and put mysql into it, but then i found the buffer pool option and i hoped it would solve my problem. I hope someone have some ideas what to do or what i missunderstand. Best regards .


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My husband and I threw a party for Navroze at home and ordered the full Navroze menu along with prawn kebabs and patra ni macchi. The food was really excellent and it was a pleasure to liaise with Darayus to do the ordering. One of our friends was a fishitarian and Maharukh kindly prepared a separate pulao for him and adapted the meal brilliantly. We cannot wait to order again!! Thank you for making Navroze a special one!!!
Just wanted to let you know the food was truly fabulous & delicious. Everything was just brilliant and our guests really enjoyed it. Thank you for your efforts for the Bhakras too
This review has taken some time but here it is: A month ago, I had the divine pleasure to eat some of Mahrukh's famous specialties and as always, her excellent culinary delights have left me dribbling shamelessly till today at the mere thought of it! Dhansak and Kebabs are simply out of this world. Dar ni Pori summoned the tooth-fairy at the oddest of hours. The Vasanu was outstanding and had just the right amounts of condiments and ingredients to give it that perfect taste and texture. I was left pining for more at the end of it all and I hugely recommend everyone reading this to give Mahrukh's Kitchen your next big food order - you won't be disappointed, and I guarantee y'all will coming back for more!! Two thumbs up and a five star hit from these neck of the woods 🙂
Delicious dhansak ni dar and kebabs. I enjoyed the dar ni pori with tea of course - Parsi pori with a British twist. Wow, enjoyed everything.
The Parsi dar ni pori was delicious and perfect with tea.
Ordered from Mahrukhs Kitchen. Everything from the chicken pattice, chicken farchas, chicken cutlets, dhan dar patiyo, moghlai chicken and fried okra was absolutely delicious. Give it a try, you will not be disappointed.
Thanks very much Mahrukh, fantastic, fantastic food. Everything was perfect.... My wife said that the fish was perfectly cooked !! .. just correct!
Fabulous food! The chutney and egg pattice were outstanding as was the lamb pulao! Already recommended to my friends!
Mahrukh and Darius delivered an amazing catered event for us at home. All our guests were delighted with the quality and quantity of food. Every single item on the menu was delicious. Thank you to both of you.
Delicious - Thats the one word to best describe Mahrukh's Cuisine.
Delicious, delicious - Then why repeat it 3 times?
Because it's the home cooked wholesome food you want to have again and again. Wish we lived here in London to enjoy all your delicacies more often.
Thank you so much.😘
The fried Mackerel was out of this world and chapattis are best I have eaten in a long time. The lamb cutlets and biryani are very good - maybe a little more spicey would be excellent. We enjoyed all of the above. Thanks a million.
I just ate one dal ni pori after opening the box. Its amazing, everything was delicious.
Everything was yummy! Dal-ni-poris were whole and tasty. Will definitely order again and spread the word. Best wishes for the future
Thanks so much for the food. It was really nice and the Farchas were gobbled up. I had Lagan nu Custard after ages.
Thank you so much for a wonderful lunch today.
Thanks for the lovely, lovely food.
Everyone who ate the sali chicken and lamb curry loved it. Other items were also tasty.
The guests loved all items and by the way mutton curry was very good - my favourite. Thanks


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High-grade cannabis, steroids seized in Laidley raids
LAIDLEY police executed two search warrants last Thursday as part of Operation Lockyer Harvest.
During the search of a Regency Downs property, police seized 14.2kg of high-grade hydroponic cannabis, steroids and an ATV.
A 42-year-old Regency Downs man was charged with one count each of supply cannabis, possess cannabis exceeding the schedule, supply steroids, and possess steroids.
He will appear in the Gatton Magistrates Court on June 18.
During a search of a property at Hatton Vale, police seized a drug utensil and jewellery believed to have been stolen or unlawfully obtained, and charged a 43-year-old Hatton Vale man with one count each of possess dangerous drug (oxycodone) and possess tainted property.
Officer in Charge of Laidley Police, Acting Senior Sergeant Dan Curtin, said it was a timely reminder for criminals in the area.
"If you intend on supplying drugs in the Lockyer Valley, you will be targeted by police who are actively investigating these offences and prosecuting persons who jeopardise the safety of the community," Snr Sgt Curtin said.
Anyone with information is encouraged to contact Crime Stoppers on 1800333000 or Laidley Police on 54668000.


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Ok, so I'm over at Dictionary.com looking up a word to make sure it's spelled right. Turns out "hoard" does not have an "e" on the end. I think it looks better with the "e", but oh well. Anyway, this little box is at the bottom and it says "What is Ghosting?" Now, I've heard... Continue Reading →
Photo File Chaos
I really hate that I can't seem to keep up with all of the fun challenges & prompts on WP that I want to participate in. I would love to be able to spend more time writing, but it seems like other things get in the way and I have to deal with them. Or else... Continue Reading →
COB- wk 29
Cee's Oddball Photo Challenge- week 29 Well, boy howdy, it seems I can't keep up with anything these days. I missed week 28 of the COB challenge. Now I'm trying to catch up with week 29. I did finally find some stuff that might be sort of interesting. This is literally, a wall of money.... Continue Reading →
Control fear
Cowardice. It's not the same as just plain being afraid. Dictionary.com says "lack of courage to face danger, difficulty, opposition, pain, etc.". Seems to me it's about what you do about being afraid. According to Ernest Hemingway: "Cowardice, as distinguished from panic, is almost always simply a lack of ability to suspend the functioning of the... Continue Reading →
COB- Week 27
I'm pretty proud of myself for getting to this within the actual time frame. Yay! For Cee's Oddball Challenge-week 27 I figured I'd post this picture of a broom. Yep, a broom. Just your ordinary angled sweeper. Or is it? Maybe not. It's not the greatest photo, but it's odd in two ways. Just a... Continue Reading →
Black Cat, Blue Sea Award
Awk! The lovely lady at A Sunken Thought has nominated me for this award! I'm still a newb so I'm not really clear on these award things but it's really nice that she thought of me. I hope I get the protocols right on this. I don't know what a black cat and a blue sea... Continue Reading →


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Does that great BART toy come with accessories?
Nina Zhito of Novato sends word of a BART tweet about "squishy" BART car toys on sale in the customer service department at the Lake Merritt Station: "Today we sold more than 10 percent of our train toys in stock. We still have hundreds left, but they are selling pretty fast. It's on sale from M-F 7:30 a.m.-5 p.m. And please ... stop asking us if the train comes with peepee, poopoo, needles and other gross things. The answer is always no."
Furthermore, in response to musician Jamey Brzezinki's comments about the beauty of BART wheels' screeching, Ken Perkins mentions another sound that intrigues him: "I've had two MRIs in recent years ... and each time as I lay listening to the very loud rhythmic banging and buzzing of the machine, I think some DJ should record and remix these remarkable percussion sounds."
Meanwhile, musician and teacher Jan Jones was struck by the screech, too, particularly "the C to C octave each train 'sings' as it leaves the station." She asked BART engineers why it happened, and her translation of the explanation is that as the motor revs up and electronic frequency is increased, "pulse width modulation" results. "From zero to 3 mph the sound is C5 (one octave above middle C on the piano) to C6 (two octaves above middle C). Sounds lovely and cheerful."
Of course, you've already read about the San Francisco Symphony's maestro-designate, Esa-Pekka Salonen, whose appointment was announced officially early on Dec. 5. That evening, however, the San Francisco Symphony invited supporters and music lovers to a razzle-dazzle introduction — Champagne and nibbles included — in the Soundbox.
The many expressions of excitement were augmented by dramatic graphics (the conductor silhouetted against the skyline), thank-yous to members of the search committee, an onstage Q&A with Salonen, and a collection of video welcomes from Bay Area superstars (beginning with Mayor London Breed, of course, and including maestro Michael Tilson Thomas, composer John Adams, empress of sound Helen Meyer, Symphony trumpeter Mark Inouye, SFMOMA's Neal Benezra, Warriors coach Steve Kerr and The Chronicle's own Joshua Kosman).
They know how to put on a concert over there at Davies Hall, but they also know how to put on a show.
•Reader M.K. read the fine print in a Vogue profile of billionaire Tom Steyer. The profile pictures the activist and Trump critic (to put it mildly) with his family, and includes written depictions of family fun. But tucked into the story is a note that as it went to press, Steyer informed the editors that he and his wife "were going to try living apart. They will, however, remain a family and work together on the dream of justice that consumes them both," wrote Rob Haskell.
•Allen Zebrowski describes seeing/hearing Laurie Anderson performing her late husband Lou Reed's "The Drones" at Grace Cathedral. "It was as if 'The Drones' was like Gelug Tibetan monks, the Tuvan Throat Singers and György Ligeti were all part of a David Lynch soundtrack. This was an only in San Francisco experience."
This year's Christmas kerfuffle, all wrapped up with a big bow on top, is about the playing of "Baby, It's Cold Outside," a 1944 Frank Loesser song that has fallen into disgrace because of the #MeToo movement. Radio stations including San Francisco's KOIT have announced that they will no longer play the song, though KOIT ultimately decided to let its listeners decide the song's fate.
Piano man Abe Battat — an old-fashioned guy who's played plenty of love songs during his career — told me about this first, and seemed incredulous about the fuss. "We used to call it 'sweet talking,'" he emailed. "Wake me when the book burning begins. We can start with Nabokov and work our way down to Spillane."
Mike Lano suggests that there are plenty of other songs that might be banned, the Police's "Every Breath You Take," for instance. He says that he and his wife are "standing up," however, "for the classic 50-year-old Rudolph CBS special," although others "are calling for it to be yanked because of the reindeer game bullying aspect."
"You know, I don't think this was what they had in mind when they gave us the scholarships."
Woman to fellow players of dominoes, overheard at the UC Berkeley Student Learning Center by Peter Hagen
Leah Garchik is open for business in San Francisco, 415-777-8426. Email: firstname.lastname@example.com Twitter: @leahgarchik


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Strategies to operating from the retail food sector are invariably changing. This runs specifically true in the supermarket space. Today's informed people are increasingly demanding quality, fresh, and innovative foods. Additionally, these consumers also demand convenience be served along with these first-rate products.
More grocery products are being bought at non-traditional food retailers. Included in this are Wal-Mart Stores Inc., Costco Wholesale Corporation, along with pharmacies/drugstores, and specialty alternative grocers.
How are traditional grocery stores – chains and independents – addressing the twin issues of freshness and convenience? Listed below are ways they're attempting to grow sales through serving their customers better:
1. Locally sourced products. It's really a considering the fact that products sourced locally will probably be on supermarket shelves as well as in supermarket counters quicker. Same-day produce and dairy deliveries from local suppliers ensure customers receive their favorite meals fresher.
Furthermore, today's savvy consumers want to know wherever their foods are received from. This allows these phones quickly trace their products origins whenever they experience any difficulty with them. Hence, locally sourced could be the new idea, which food retailers are stored on board with in order to meet customer demands.
2. More specialized departments. Fresh products in grocers are coming increasingly from very specialized departments. These include artisan bakeries, market fresh seafood and fish departments, gourmet cheese departments, and create departments offering more organic produce.
Artisan in-store bakeries (with products baked fresh daily) are providing breads along with other goods with unbleached flour and healthy whole grains. Specialized departments focusing on all-natural merchandise is quitting products containing MSG. Moreover, they're catering to consumers' wishes for low-sodium, low or no sugar, as well as gluten-free products.
3. Clean food. Industry is demanding 'cleaner' food. This implies products with limited ingredients. Nonetheless, these limited ingredients must be first-rate, without preservatives and additives. Consumers desire to know how their vegetables and fruit are grown and processed. They would like to know if the meat they're buying is grain or grass-fed and whether it contains antibiotics or chemicals. Supermarkets are increasingly stocking meals that meet consumers' needs over these areas.
For details about grocery stores opening times you can check our new web page.


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Cygnus Memory Foam Wheelchair Cushion
The Cygnus Memory Foam Wheelchair Cushion incorporates the latest technology in memory foam to create the ultimate level of comfort. This highly advanced memory foam wheelchair cushion features visco elastic properties designed to improve the overall sitting experience for users.
Featuring an extra thick layer of temperature sensitive memory foam, the Cygnus Memory Foam Wheelchair Cushion moulds effortlessly to any shape when pressure is applied. A high density foam base adds to the level of support which the Cygnus Memory Foam Wheelchair Cushion provides. All of these properties work in unison in order to create one of the most superior feeling wheelchair cushions to date.
Cygnus Memory Foam Wheelchair Cushion Features.
- Temperature sensitive memory foam top layer to aid in reducing pressure on a user.
- High density foam base for added levels of support.
- Incorporates visco elastic technology. Ideal for visco elastic therapy.
- Easy to clean, easy to remove, polyurethane coated nylon cover.
- Multi-use suitability. For use in wheelchairs, armchairs or cars.
Find Comfort With The Cygnus Memory Foam Wheelchair Cushion.
Temperature sensitive memory foam is perfect for use in wheelchair cushions. This revolutionary foam reacts to body heat in order to appropriately mould to the unique shape of a person. Due to the level of heat which our bodies produce, this unique memory foam detects body pressure is applied. As pressure continues to be applied to the wheelchair cushion, the Cygnus adapts quickly in order to provide long lasting support.
The Cygnus high density foam base provides exceptional levels of support due to it's close cellular structure. Whilst the top, temperature sensitive memory foam layer molds to a users unique shape, the high density base layer works to retain it's shape to a greater extent. The combination of these two layers works to provide both support and comfort like no other.
The correct level of support is essential for those using a wheelchair cushion. Incorrect support may prove to lead to adverse health effects. These include such things as pressure ulcers, lumbago and general damage to the neck and/or spinal area. Pressure ulcers have shown to be a common complaint amongst people in wheelchairs that use substandard wheelchair cushions. These, if left untreated can lead to serious (sometimes fatal) effects on an individual's health. The best course of action is of course to combat the route of the problem. By purchasing a Cygnus Memory Foam Wheelchair Cushion, you'll be reducing the risk of pressure ulcer development.
Suitable For Healthcare and Homecare Use.
At GB Foam Direct, we aim for every wheelchair cushion produced by us to be suitable for individuals no matter their situation. We put a great deal of thought into all of our wheelchair cushion designs and test them vigorously. This way both we and you can be assured that our products are suitable for you, no matter your needs.
The Cheapest Yet Best Wheelchair Cushion On The Market.
At GB Foam Direct, we're proud to be the manufacturer and seller of quality foam products! As we don't have to pay an outsider company to produce our products, we save money in the manufacturing process. There's no middleman when you purchase from us. Everything we produce is made in our state of the art factory in High-Wycombe. This means that we can pass money we save on to you the customer. As a result, this means that you can be assured that you're receiving a high quality wheelchair cushion, without spending the Earth. We believe that everybody should have access to the best quality products which is why our prices are so competitive.
Cygnus Memory Foam Wheelchair Cushion Technical Specifications
|Risk Category
|High Risk
|Weight Limit
|35 Stone – 222 kg
|2 Years
|43 cm x 43 cm x 7.5 cm (17" x 17" x 3") Variable Sizes Available Upon Request
|Foam Density
|Memory Foam – GBV60/135 – 60 kg/m3 Nominal Hardness – High Density Base Foam – GB50/230 – 50 kg/m3 Nominal Hardness – 230 Newtons
|Fatigue Class
|Fire Retardancy
|Cushion Weight
|1 kg
|Hypochlorite Solution compatible
|1,000 ppm diluted or 0.1% (or to be used in conjunction with local infection control guidelines)
Latest Cygnus Memory Foam Wheelchair Cushion Reviews
Karen Coyle
Extremely comfortable gets used all the time.
Martin White
I like how easy this is to add and remove it means I can use it in multiple places.
Ian Neale
Was hesitant about the asking price, but after receiving it I can see that it's worth every penny.
Nicholas Ellam
Fast delivery as promised.
Nathan Hartigan
Picked this up for my mother after she injured her knee. She was very grateful as am I.
Gerald Keenan
A brilliant cushion that is well worth the price tag. I could tell the quality straight away.
Clive Ward
Lovely and comfortable.
Gillian James
a very nice cushion thank you.
Simon Staples
I've recently had knee surgery and as a result, have been confined to a wheelchair for the most part. Really wasn't getting on well with it, sore lower back and bum so decided to get a cushion to help fix this. My chair is now really comfortable thanks to this cushion. Thank you.
Christine Niven
Nice and high quality. Very supportive.
Malcolm Hayward
Very fast delivery.
Helen Clifton
I've been told by mother to tell you that the cushion is very comfy and to say thank you, bless her. Thank you GB Foam.
Rachel Bourne
Pleased with this wheelchair cushion it seems to be high quality.
Michele Jessop
Great quality and very fast delivery times.
Sally Hiley
Super Duper Thank You!!
Gail Davis
Getting on very well with my new wheelchair cushion, thank you.
Margaret Briggs
A well-made wheelchair cushion makes for more comfortable sitting during long periods.
David Herbert
Happy with the price of this. The quality is very good for how much I paid.
Arthur Perry
Fast delivery and a fair price.
Aaron Richardson
very good product, simple and easy to use and make life so much better for our carers
Ruth Lee
Fantastic product, quick delivery and excellent service.
Andy Roberts
excellent product, excellent service.
Laura Johnson
Very happy with this product.
John Long
very quick delivery and with a large order too, thanks
Sharon Cook
Easy to order an quick delivery, thanks GB
Elizabeth Adams
Quick delivery and excellent service.
Kathleen Roberts
this really helped with my posture when I broke my hip, I just seemed to sit up that little bit straighter
Sandra Watson
Tested a few of these and the ones from GB seem the best at the best price
Amy Howard
Quick and easy delivery and a good price - nice work guys
Gloria Peterson
Delivery was fast and service was great.
Philip Henderson
Nice and comfortable, takes the edge of during the day.
Julie McKay
Perfect. A well made cushion at a very nice price.
Valerie Gray
Thank you I bought one of each. I prefer this one for the most part, but the other is still very good as well.
Peter Fleming
Im very happy with this cushion. Thank you.
Lois Taylor
Fits the chair well. Would recommend.
Mr J Owens
Arrived the day after I ordered it. Happy with the quality and the price I paid for it.
Hayley Hogan
Arrived next day and fits well. Would recommend to others.
Oliver Osborne
This is a very comfy wheelchair cushion, I would recommend it.
Tom Hanson
Well made. I've been using this for about a week now it's already made quite a bit of difference.
Freya Slater
Robert Baker
Arrived the next day as I was told it would be.
Alan Miller
Great! Very comfy to sit on and arrived the next day
Related Products
Why Choose GB Foam For Your Foam Cut To Size?
Our factory is equipped with the latest CNC cutting technology and throughout the years we have employed the most talented freehand foam cutters in the industry. Many members of the team have worked for the company for several decades and their attention to detail and quality control is something that only comes with years of knowledge and experience.
We have many customers who started with us in 1976 and are still working with us today, which we like to think reflects on our vision to be the most dynamic foam converter in our industry. For us no job is too big or too small. We offer the same level of service and delivery whether you are a retail customer ordering one piece of foam from home, or a large manufacturer ordering daily.
40 Years In BUsiness
GB Foam have been offering foam cut to size from our factory since 1976.
Hand Made In THe UK
We employ the most talented freehand foam cutters in the industry.
ISO 9001 Quality
Our team work to the ISO 9001 quality standards to guarantee only the best
Super Fast Delivery
All orders placed before 11:00am will be despatched for next working day delivery
5 Year Guarantee
Our foam comes with a 5 year guarantee against faults in manufacture.
Flame Retardant
Our entire range of foam exceed UK safety and flammability standards.


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HGTV Analysis
HGTV is one of the most consistent programmers on the cable spectrum, but the line-up went through some changes in the second half of 2012, and more change is hitting at the beginning of 2013.
HOUSE HUNTERS and HOUSE HUNTERS INTERNATIONAL remain the key component of primetime, tethered to 10 and 10:30 from Monday through Saturday.
LOVE IT OR LIST IT, which is basically HOUSE HUNTERS with a spin, is a much-needed scheduling staple, giving the HOUSE HUNTERS some relief. LOVE IT calls Monday home, but can fill in on other days of the week, and has replaced the iconic Design Time Saturday night. The design shows consistently under-performed real estate and construction programming, but seemed safe and somewhat under the radar on Saturday nights, where Design Stars and HGTV personalities were born and bred. The night has gone from the lowest rated to one of the top-rated of the week.
"The Guys of Wednesday Night" still reign, with the help of the PROPERTY BROTHERS and their spin-offs and the KITCHEN COUSINS and their spin-offs.
Thursdays were the power real estate brokers with SELLING NY, then LA, and LONDON. NATURAL BORN SELLERS joined the fray in August. But they are gone, and HGTV has been rotating repeats of Wednesday night fare and introducing new programming in an attempt to fill the hole and find the next hit.
Fridays are usually filled with a mix of seasonal specials, which have become a breeding ground for new programming.
And finally, Sundays were the long-standing home for Mike Holmes and his various programs…HOLMES ON HOMES, HOLMES INSPECTION and GREAT AMERICAN HANDYMAN. But the programming was fading and the dual male/female audience did not match the rest of the schedule. By the end of September Mike and his programs were gone. HOLMES MAKES IT RIGHT is airing on HGTV Canada, and the DIY network, but not on HGTV. In the meantime, Sunday has been acting as more of a marquee night, and the strategy seems to be catching on. In November HOUSE HUNTERS RENOVATION found a permanent home at 10PM. In first quarter aspirational/escapist programs (HAWAII LIFE and ISLAND HUNTERS) made an impact.
As the year progresses, HGTV plans to continue aggressively rolling new programming into the line-up, with everything from compelling real estate shows to engaging renovation series to follow docs, workplace docs and character-driven programs. The network has indicated a desire to go a bit more edgy than they have in the past. "Anything that fits across the spectrum of "home" - in a way that's never been presented before. Shows with a twist, a different POV, a bit of edge, and that are full of passion and imagination for an upscale audience is welcome fare. Our audiences crave high-energy experts and programs that are fun, informative, and most importantly, entertaining." (HGTV)
Live Plus Same Day Primetime Ratings Comparison / March 2013 vs. March 2012 (% Change)
Source: The Nielsen Company's National Television Audience Sample
MARCH 2013: Primetime ratings have leveled out from their January peak, but are still at the top of the HGTV ratings spectrum. There was no change in bottom-line primetime women 25-54 ratings vs. last month, and they are up 3% compared to last March (which was a strong ratings month).
HGTV has the unique advantage of having a strong base of steady performers on the line-up, allowing room to rotate in a relatively new programming with a decent margin for error. The network is also flexible enough to accommodate a break-out hit.
HOUSE HUNTERS and HOUSE HUNTERS INTERNATIONAL are the steady base – airing Monday through Saturday from 10 to 11 the two programs receive the most real estate, and usually the highest ratings on the primetime line-up. While they both dropped 8% of women 25-54 ratings vs. last month, they retained ratings vs. last year and their place at the top of the ratings ranker.
Wednesday night's PROPERTY BROTHERS and KITCHEN COUSINS have become a franchise for HGTV, with new programming spinning off the base. COUSINS ON CALL was on the line-up this month, but it was not met with a lot of ratings success. UNDERCOVER OVERHAUL, another program featuring the cousins, is slated to launch in October.
Break-outs that did draw good numbers, and subsequently a bigger presence on the line-up, include LOVE IT OR LIST IT, FLEA MARKET FLIP, HOUSE HUNTERS RENOVATION, SCORING THE DEAL and HAWAII LIFE. LOVE IT went from one run a week last year to 4 runs a week this year, bringing ratings success to both Monday and Saturday nights. FLEA MARKET FLIP was back for a second season this March, and despite its unenviable Friday night time slot, it rose to the top fifth of the monthly W25-54 ratings ranker. HOUSE HUNTERS RENOVATION has been in place on Sunday nights at 10, nicely filling in for its parent programs. SCORING THE DEAL and HAWAII LIFE have already received renewal orders. In fact, HAWAII LIFE launched in January, and has already received two orders for more episodes. The network attributes both programs' success to their voyeuristic nature, a theme that has always resonated with HGTV's audiences.
WEST END SALVAGE, YOU LIVE IN WHAT? and REHAB ADDICT are newer programs on the cusp of success. AUCTION AGENT debuted on Friday nights this month, and still needs time to percolate.
Tuesday night's INCOME PROPERTY, BUYING AND SELLING and PROPERTY VIRGINS are older programs that are starting to show their age. Fortunately, the network is well set up to fill the gaps. Friday nights are a breeding ground for new programs. Specials are rotated in, and those that pop are often turned into series. EXTREME HOMES followed that model, and this month it was drawing strong numbers on Sunday nights.
It looks like HGTV is well set up for ratings growth. The once-staid network has learned to be nimble in the fast-changing marketplace, and has become a fertile breeding ground for successful franchises.
The television industry's top news stories, analysis and blogs of the day.
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E-Cormmerce Website by Jade Choi
Jade Choi Designs The Noritake E-Cormmerce Website
Jade Choi, the architect of the awarded work Jade Choi's Noritake e-cormmerce website explains, Made a year ago, this was a flagship flat design project when flat design was not trending. This design features tile-formatting for products & the whole site's grid system. I also created the unique branding in the footer with subtle, yet detailed typography. This website concept was to create a simple, elegant design that made sense using appropriate whitespace and flat design elements. .
E-Cormmerce Website by Jade Choi Images:
End of the article, click here to go back to previous page, or alternatively go back to Design Cool homepage.


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Today I have a Guest Reviewer. He is giving his opinion on an important non-fiction book that he has read.
Now I will hand things over to my husband, Ted Wilder.
Title: Jesus and the Jihadis: Confronting the Rage of ISIS, the Theology Driving the Ideology
Author: Craig A Evans and Jeremiah J. Johnston
Pages: 176
Year: 2015
Genre: Non-Fiction
Publisher: Destiny Image
Format: Paperback (also available in eBook)
Note: I received a free copy of this book through The Book Club Network in exchange for my honest opinion.
About the book:
The book that Christians want and need for this urgent hour in history.
As ISIS dominates news headlines, attention is given to the terrorist group's ideology… when the true motive of their mayhem is actually revealed in their theology!
Major General Michael K. Nagata of the Special Operations forces in the Middle East explains that "we do not understand the movement… and until we do, we are not going to defeat it."
The key to defeating ISIS' regime of terror is understanding its theology.
This is why two leading Biblical scholars offer this go-to guide to understanding ISIS' distorted theology. Through fresh historical and Biblical insights, discover how ISIS' acts of violence, terrorism, and persecution impact your life and your faith today.
Get revealing answers to questions such as:
How did three faiths come out of one man – Abraham?
Who does ISIS utilize social media and technology for terrorist propaganda?
Is ISIS Islamic and would Muhammad himself join this group?
How do the Gospels and the Qur'an see Jesus differently?
How does Biblical history address the development of ISIS?
The question millions are asking is Why? Why the hate? Why the persecution? Why the murder? To find the answer, you will trace the origins of ISIS' radical theology and discover why these acts of terrorism are happening, what they mean, and where they are taking us.
Ted's review:
A no-spin look at ISIS.
This book may not be an easy read. It is essential though if you are to understand ISIS, and all the other Islamic terrorist groups. This book is loaded with information, laid out in a logical format with lots of footnotes backing up every fact. It hits hard without being a "hit piece."
This book has several sections covering different aspects of the issue. First an introductory chapter presents the problem. Then there are several chapters on the origin of Islam – a must read.
The story of the Bible is fully substantiated by archaeological evidence. There is no refuting the evidence. This is why ISIS is hell bent on destroying the ancient antiquities which refute their faith. Then the author gives us a fascinating comparison of the Bible and the Qur'an. And finally we get a great history of ISIS in modern times.


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Cora is changing the experience of womanhood—for all women, everywhere. With every product you purchase, we give period pads and health education to a girl in need. Learn more about Cora's products and mission here.
Named by Women's Running as one of twenty women who are changing the sport of running and the world and by The Root 100 as one of the most influential African Americans ages 25 to 45, Alison is an endurance athlete, activist, and mental health counselor. Alison is the founder of Harlem Run (an NYC-based running movement) and Run 4 All Women (an initiative that has raised over $150,000 for Planned Parenthood), and just launched the podcast Finding Meaning (on the RUN). Alison is currently featured in Under Armor's latest global campaign, Unlike Any, which celebrates and honors the unprecedented achievements of female athletes that rise above gender comparisons and stand on their own as marvels of athletic prowess. Alison started running distance after a period of depression, and, over the past 5 years, has been able to Find Meaning on the Run. When Alison is not running, she is working to resolve and speaking passionately about issues related to women and girls as well as mental health. Alison recently wrote the foreword for "Running is My Therapy," by NYTimes best-selling author Scott Douglas.


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Clean & Safe property. Free cancellation up to 5 days before arrival. Pay only 30% to reserve.
LV Premier C.Ourique CO1 is located in upmarket neighborhood of Campo de Ourique near Amoreiras shopping mall. The neighborhood is often described as a foodie paradise with many restaurants headed by talented chefs, the gourmet market with upscale food and wine carts. It is a mini city within the city with all services, shops and lots to see. This (high) ground floor apartment is reached through 10 steps, and it features the bedroom in the back facing a quiet courtyard, plus the living room and a small but fully equipped kitchenette. The open plan/loft apartment features AC and heating, and is located in a traditional centenary building which has been renovated in the last 3 years. The Rato metro station is 15 min away metro station, with buses and the famous 28 tram nearby. 75644/AL
LV Premier C.Ourique Apartments CO1 is a ground floor open concept loft style 1 bedroom apartment with one bathroom. Enjoy a taste of a traditional, yet sought after neighborhood in Lisbon right from your window. Time to sleep?- enjoy our very own LV Premier signature beds with comfortable new mattresses, crispy linen and soft comforters.
The living area is open space with the dinning area and the kitchenette. It features a large TV. The bathroom was just remodeled and has a modern shower enclosure. The kitchenette is fully equipped. We provide soft bath towels, toiletries for your first day and of course a hair dryer. Bedroom and living room have heating and AC units.
The building, located in a parallel to the main street in Campo de Ourique (Ferreira Borges) combines proximity to all services with a quiet street feel.
– Open plan/ Loft style
– AC, Heating
– Dishwasher, Washing Machine, Tumble Dryer
– Kettle, Toaster, Coffee maker, Food Processor
– Microwave, Oven
– Hair Dryer, Complimentary Toiletries
– Premium Bed Linen and Towels
Campo de Ourique is of the few areas of Lisbon that survived the 1755 earthquake and tsunami with only minor damage and, as a consequence, became a area of election. In the second half of the 1800s, the area saw a new demographic influx, with the development of grid pattern neighborhood anchored in rua Ferreira Borges. Many notable Portuguese authors, including Fernando Pessoa, lived here. Today it is the home of many shops and restaurants, has a well loved romantic garden- Jardim da Parada, the Mercado- market with gourmet food and wine stalls, and one of the most recognizable cemetery of the city- Prazeres. It is minutes away from the upscale Amoreiras shopping mall and from the neighborhood of Rato and Estrela with both Basilica da Estrela and Jardim da Estrela as popular attractions. The famous number 28 tram makes the connection to the Baixa/Downtown area as well as the other traditional Lisbon neighborhoods of Bairro Alto, Chiado, Graça and Alfama


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38th Annual Quality Conference #BOSCON2019
"New Quality in a New World: Innovating Quality in a Digital Era"
BOSCON is an annual quality conference hosted by ASQ Boston. BOSCON is the section's signature event where national and international quality professionals hear speakers discuss different quality topics and network with them. The conference focus for 2019 is innovation in quality as a survival strategy in a Digital Era to adapt to the exponential change of technology.