Advanced drug delivery applications of layered double hydroxide

This review first surveies the characteristics （chemical composition, structure, synthesis and intercalation properties） of layered double hydroxide （LDH）, alternaotely known as anionic clay or hydrotalcite-like compound, and then provides the production methods of some eco-nanomaterials using LDH. Usually, LDH is characterized by its easy preparation under mild conditions, formation of nano-sized plate-like particles and unique properties such as high anion exchange capacity and good biocompatibility. In addition, the delamination of LDH has been achieved recently by chemical techniques to produce LDH nanosheets. Based on these features, the production examples of functional organic-inorganic nanohybrids, polymer-inorganic nanocomposites, and new carrier materials of drug delivery system from LDH are reviewed together with the recent results of our LDH research works.

Layered double hydroxide (LDH) is prepared conventionally with bivalent and trivalent cations. We recently reported that the preparation of Zn-Ti LDH consisting of bi and tetravalent cations is possible through the decomposition of urea. In this study, Zn-Mo LDH consisting of bi and hexavalent cations were prepared and reacted with organic monocarboxylic and dicarboxylic acids. Interlayer spacing of the prepared LDH (Zn-Mo-CO3) contained carbonate anions between the layers was 0.72 nm. The spacing was small compared to usual LDH (Zn-Al-CO3) of 0.76 nm in the case of carbonate anion as the guest. Also, TG analysis indicated that the electrostatic force between the Zn-Mo layers and carbonate anions was larger than those of Zn-Al LDH. Certainly, the carbonate anions in Zn-Mo LDH decomposed at 260°C while they in usual LDH decomposed at 230–240°C. ESCA showed that Mo5+ had changed to Mo6+ through the preparation procedure. These results showed the preparation of layered double hydroxides consisting of bivalent and hexavalent cations. By the intercalation of Zn-Mo LDH with suberic acid at 60°C, a sharp peak was observed at 1.06 nm and the peak of LDH itself (0.72 nm) disappeared. This result has suggested that the intercalation of organic acid into new LDH was performed completely.

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Layered double hydroxides: A brief review from fundamentals to application as evolving biomaterials

Application of layered double hydroxides (LDHs) in corrosion resistance of reinforced concrete-state of the art

Layered double hydroxides (LDHs), well known as anionic clays or hydrotalcite-like compounds consist of positively charged layers. Net positive charges on the layers are balanced by exchangeable anions along with water molecules in the interlayer space. In the present research, the potential for use of Ca/Al-LDH as local hemostatic agent is evaluated in vitro by measuring the coagulation time of human fresh blood in the presence of LDH powder. Crystalline Ca/Al-LDH powders required for these experiments were synthesized via a co-precipitation method followed by a controlled hydrothermal process using calcium nitrate and aluminum nitrate as starting materials under certain synthetic conditions such as time and concentration. XRD and SEM analyses were utilized to characterize the synthetic powders. XRD and SEM results demonstrate the presence of a crystalline pure Ca/Al-LDH with hexagonal morphology. In order to investigate the biocompatibility of the samples, culture techniques were employed using mouse fibroblast cells (L929) as reference cell line. The results reveal that LDH powder can accelerate the platelet aggregation and the formation of blood clot. Moreover, the samples show good cell proliferation and high cell viability to L929 cell line compared with negative control sample. These results demonstrate that these layered materials are suitable candidates for using as local hemostatic agent to hemorrhage control and can reduce blood loss in lethal injuries. INTRODUCTION Uncontrolled bleeding and consequent hemorrhagic shock are leading causes of death in many injuries and early hemorrhage control can improve outcome [1-2]. In minor accidents, the bleeding may be controlled by the body's own blood clotting mechanisms. But in more severe wounds, additional controls such as applying pressure or using of absorbent dressings or pads are required. But these methods may be ineffective for severe bleedings or bleedings in persons with lessened blood clotting mechanisms. One efficient way to control bleeding is to use a hemostatic agent in the form of powder, foam, pad, etc. at the source of the bleeding. Limited materials are known for hemorrhage control [3]. Such an agent must be safe, rapidly effective and have good systemic and local compatibility [4]. Several fibrin-based, collagen-based, cellulose-based and gelatin-based [4-7] systems are been introduced as local hemostatic agents. While these materials are effective for control of bleeding, they are expensive. A newer local hemostatic agent –commercially named QuikClot ® is a zeolite-based powder that shows good control in many bleedings with different bleeding sources [1-2, 8-9]. Zeolites are a family of Silicates that are one of the most abundant classes of minerals on Earth. Clays are a group of inorganic materials that have structural similarities to zeolites [10]. Layered Double Hydroxides (LDHs), also called anionic clays or hydrotalcite-like compounds, are clay-like materials that show promising properties for a large number of applications. Layered double hydroxides (LDHs) have been known for over 150 years since the discovery of the mineral hydrotalcite. They are a broad class of inorganic lamellar compounds with high capacity for anion intercalation. The LDH structure -represented by [M 2+ 1-xM 3+ x(OH)2] x+ (A n)x/n·mH2Oresults from the stacking of brucite-like layers ([Mg(OH)2]) containing extra positive charge due to the partial isomorphous substitution of M 2+ by M 3+ . This positive excess charge is balanced by anions, which exist in the interlamellar spaces [1-3]. Layered double hydroxides display unique physical and Page 1 of 5

Layered double hydroxides (LDHs) or anionic clays are an important class of ion-exchange materials, well known for drug and gene delivery and several other applications including catalysis, bioactive nanocomposite, electroactive and photoactive materials. Their structure is based on positively charged brucite-like inorganic sheets with the interlamellar space being occupied by charge-compensating exchangeable anions. In spite of having a vast scope many of the applications of LDHs are restricted as their host-guest chemistry is limited to ion-exchange reactions. Recently we have shown for the first time that charge-transfer interactions can be used as a driving force for the insertion of neutral guest molecules (ortho- and para-chloranil) within the galleries of an Mg-Al LDH by forming a charge-transfer complex with aniline pre-intercalated as p-aminobenzoate anion. Here, we have performed quantum chemical calculations in combination with molecular dynamics simulations to elucidate the nature of interactions, arrangement and the evaluation of electronic and Raman spectral signatures of the chloranil charge-transfer complex included within the galleries of the Mg-Al LDH. The natural bond orbital (NBO) analysis has been used to understand the nature and origin of the unidirectional charge-transfer that lead to the unusual insertion of chloranil in the galleries of the Mg-Al LDH. The NBO analysis reveals that a considerable amount of electronic charge redistribution occurs from the p-aminobenzoate to the chloranil during latter's insertion within the LDH galleries with a very negligible amount of back donation. This work is expected to pave the way for understanding the host-guest chemistry and targeted and controlled delivery of poorly soluble drugs.

Chapter 17 - Assembly Chemistry of Anion-intercalated Layered Materials

Alkaline fuel cells (AFCs) with solid electrolytes such as anion exchange membrane (AEM) have received attention in recent years. This is mainly due to faster kinetics for oxygen reduction reaction (ORR), and the possible use of non-platinum catalyst such as nickel and silver in the alkaline fuel cells. In the traditional AFCs using KOH aqueous solution as the electrolyte, the electrolyte is very sensitive to the presence of carbon dioxide. However, in the AFCs with solid electrolyte, a degradation with carbon dioxide can be avoided. We have focused attention on layered double hydroxides (LDH) as an ion conducting material. LDHs are anionic clay and the general formula for LDHs is [MII 1 - x MIII x(OH)2][(An-)x/n·mH2O], where MII is a divalent cation such as Ni2+, Mg2+, Zn2+, etc., and MIII is a trivalent cation such as Al3+, Fe3+, Cr3+, etc., and An - is an anion such as CO3 2-, Cl-, OH-, etc. We have recently reported that the ionic conductivity of LDHs were closely related to the species of intercalated anions, LDHs intercalated with CO3 2- showed high hydroxide ion conductivity of the order of 10-3 S cm-1 under 80% relative humidity [1-3]. We also reported that LDHs were hydroxide ion conductor, and can be applied to the solid electrolyte of alkaline direct ethanol fuel cell (DEFC) [1, 3]. In a fuel cell, the formation of good triple phase boundary (TPB) in the electrodes is very important. Although Nafion acts as proton conducting ionomer and drastically improves the cell performance in proton-conductive polymer electrolyte fuel cells, sufficient materials, ionomers, to effectively transport OH-ions, have not been found in AFC at present. In this presentation, the ionic conductivity of M-Al LDHs (M=Ni, Mg, (Ni, Mn)) and M-Fe LDHs (M=Ni, (Ni, Mn)) intercalated with CO3 2-will be presented. Application of LDHs to the electrolyte or catalyst layer of the fuel cells will also be reported. LDHs stuided in the present study are found to show high ionic conductivity of the order of 10-3 S cm-1 under the rerative humidity 80%. The results in EMF measurements for a water vapor concentration cell showed that these LDHs are a hydroxide ion conductor under the humidified condition. H2-O2 fuel cells with Mg-Al and Ni-Al LDHs as an electrolyte and MnO2 as the cathode catalyst were confirmed to be operated. Alkaline-type DEFC using anion exchange membrane as an electrolyte and the electrodes with LDH as “ionomer” was also fabricated [4]. The DEFCs using catalyst layers with Ni-Al, Mg-Al, Ni-Fe, and (Ni, Mn)-Fe LDHs showed higher cell performance than the DEFC using catalyst layer without LDH. These results indicate that hydroxide ion conducting LDHs work as ionomer, and construct more favorable TPB regions in the catalyst layer.[1] K. Tadanaga, Y. Furukawa, A. Hayashi, M. Tatsumisago: Adv. Mater. 22(2010) 4401. [2] Y. Furukawa, K. Tadanaga, A. Hayashi, M. Tatsumisago, Solid State Ionics 192(2011) 185. [3] D. Kubo, K. Tadanaga, A. Hayashi, M. Tatsumisago: J. Electroanal. Chem. 671(2012) 102. [4] D. Kubo, K. Tadanaga, A. Hayashi, M. Tatsumisago: J. Power Sources 222(2013) 493.

Clay Surfaces - Fundamentals and Applications

Chapter 14.1 - Layered Double Hydroxides (LDH)

Layered double hydroxides: an insight into the role of hydrotalcite-type anionic clays in energy and environmental applications with current progress and recent prospects

Synthesis, characterization and sinterability of pure and Ni-doped nano layered double hydroxides from aluminum dross

Effect of freeze drying on characteristics of Mg–Al layered double hydroxides and bimetallic oxide synthesis and implications for fluoride sorption

As a promising candidate for expanding the capacity of drug loading in silica nanoplatforms, hollow mesoporous silica nanoparticles (HMSNs) are gaining increasing attention. In this study, porous nanosilica (PNS) and HMSNs were prepared by the sol-gel method and template assisted method, then further used for Rhodamine (RhB) loading. To characterize the as-synthesized nanocarriers, a number of techniques, including X-ray diffraction (XRD), transmission electron microscopy (TEM), nitrogen absorption-desorption isotherms, dynamic light scattering (DLS), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR) were employed. The size of HMSN nanoparticles in aqueous solution averaged 134.0 ± 0.3 nm, which could be adjusted by minor changes during synthesis, whereas that of PNS nanoparticles was 63.4 ± 0.6 nm. In addition, the encapsulation of RhB into HMSN nanoparticles to form RhB-loaded nanocarriers (RhB/HMSN) was successful, achieving high loading efficiency (51.67% ± 0.11%). This was significantly higher than that of RhB-loaded PNS (RhB/PNS) (12.24% ± 0.24%). Similarly, RhB/HMSN also possessed a higher RhB loading content (10.44% ± 0.02%) compared to RhB/PNS (2.90% ± 0.05%). From those results, it is suggested that prepared HMSN nanocarriers may act as high-capacity carriers in drug delivery applications.