Intercalation compounds of layered materials for drug delivery use. II. Diclofenac sodium

Intercalation compounds of ternary layered inorganic materials, synthetic mica (Na-TSM), with diclofenac sodium (DFS) and its drug release characteristics were investigated. Hygroscopic DFS was selected as a model drug to verify the anti-humidity and anti-oxidation of the intercalation compounds. Na-TSM powder was first mixed with the reduced-type phosphatidylcholine (H-PC) solution of chloroform or ethanol. DFS was then mixed with these solutions and heated at 37 degrees C to prepare the ternary Na-TSM/H-PC/DFS compound. A remarkable phenomenon was observed in the drug release study. The net amount of DFS from the DFS powder decreased apparently after 20 min arising from the decomposition of DFS in acidic medium. On the other hand, the net amount of the released DFS from the intercalation compound was invariant. Thermal analyses study indicated that DFS powder was hygroscopic and a significant endothermic peak was observed accompanied by a large weight loss due to the dehydration of adsorbed water from 40 to 90 degrees C. On the other hand, no significant dehydration reaction was observed in the intercalation compounds even in the sample stored under humid conditions. The present results indicated that the ternary intercalation compound was resistant to acid in addition to anti-humidity.     

Synthesis and characterization of [4-(2,4-dichlorophenoxybutyrate)-zinc layered hydroxide] nanohybrid

A new layered organic–inorganic nanohybrid material in which an agrochemical, 4-(2,4-dichlorophenoxy)butyrate (DPBA) is intercalated into inorganic interlayers of zinc layered hydroxide (ZLH) was synthesized by direct reaction of aqueous DPBA solution with zinc oxide. The resulting nanohybrid is composed of the organic moieties, DPBA sandwiched between ZLH inorganic interlayers. The nanohybrid afforded well ordered crystalline layered structure, a basal spacing of 29.6 Å, 23.5% carbon (w/w) and 47.9% (w/w) loading of DPBA. FTIR study shows that the absorption bands of the resulting nanohybrid composed the FTIR characteristics of both the DPBA and ZLH which further confirmed the intercalation episode. The intercalated organic moiety in the form of nanohybrid is thermally more stable than its sodium salt. Scanning electron micrograph shows the ZnO precursor has very fine granular structure and transformed into a flake-like when the nanohybrid is formed. This work shows that the nanohybrid of DPBA-ZLH can be synthesized using simple, direct reaction of ZnO and DPBA under aqueous environment for the formation of a new generation of agrochemical.     

Layered confinement of protein in synthetic fluorinated mica via stepwise polyamine exchange

We have developed a process to incorporate the model protein, bovine serum albumin (BSA), into the layered spacing of swelled mica. By a stepwise intercalation, the sodium form of synthetic fluorinated mica (Mica) was first exchanged with the poly(oxyalkylene)-diamine salts (POA-amine) through an ionic exchange reaction and then the BSA embedment. The first step of the Mica space expansion from the pristine 12 A to 18-93 A was affected by hydrophobic POP-amines (POP2000 of 2000 g/mol and POP4000 of 4000 g/mol M(w)) and the hydrophilic POE2000 that intercalated Na+-Mica to afford different basal spacing (39, 93, and 18 A, respectively). The POA modification was necessary for the BSA intercalation and resulted in an uncompressed form of protein conformation in the layered confinement (XRD d spacing = 60-71 A). For comparison, direct intercalation rendered only low d spacing (30 A), in which BSA was embedded in a compressed conformation. The BSA-mica complexes were characterized by X-ray, TGA, and solution analyses. The stepwise process provides a new method for embedding large protein molecules into the clay layered structure generating protein/layered silicate complexes.     

The functional layered organosilica materials prepared with anion surfactant templates

A novel strategy for the synthesis of layered organosilica is demonstrated. The ionic interaction between the anionic group of a surfactant (sodium dodecyl sulfate) and the cationic organic group of an organosilane (3-aminopropyltrimethoxysilane, ATMS) under acidic conditions was utilized to create a layered organosilica at room temperature. The inorganic part of the organosilica layer was an Si-O hexagonal sheet, and organofunctional groups were alternately arranged on both sides of the sheet. The layered structure of the ATMS organosilica was retained after the removal of the surfactant with chloride anion. The properties of the layered ATMS organosilica were investigated. The layered ATMS-Cl organosilica is stable and possesses a definite layer structure in water or ethanol. Various kinds of anions can be intercalated in the interlayer space of the layered ATMS organosilicas and the layer was expanded dependent on the intercalated anions. The structure of the layered ATMS organosilica was well retained during the intercalation processes.     

Selective adsorption of mercury ion by mercaptocarboxylic acid intercalated Mg-Al layered double hydroxide

Intercalations of mercaptocarboxylic acid and dithiodicarboxylic acid in Mg-Al layered double hydroxide and their adsorption properties for heavy metal ions were examined. During the intercalation of mercaptocarboxylic acids, mercapto group was oxidized, and the corresponding dithiodicarboxylic acids were intercalated in the interlayer space of Mg-Al layered double hydroxide. The intercalation compounds adsorbed mercury and silver ions effectively, whereas there was no adsorption of copper ion practically.     

A novel organic intercalation system with layered polymer crystals as the host compounds derived from 1,3-diene carboxylic acids

A new type of organic intercalation system using poly(muconic acid) and poly(sorbic acid) crystals as the host compounds is described. The layered polymer crystals as the host are derived from benzyl-, dodecyl-, or naphthylmethylammonium salts of (Z,Z)-muconic or (E,E)-sorbic acids by topochemical polymerization. The subsequent solid-state hydrolysis of the resulting ammonium polymer crystals provides the corresponding carboxylic acid polymer crystals. When alkylamines are reacted with poly(muconic acid) or poly(sorbic acid) crystals dispersed in methanol at room temperature for a few hours, the intercalation proceeds to give layered ammonium polymer crystals via solid-state reactions, in which the polymers maintain a layered structure throughout. The interplanar spacing value of the polymer crystals changes according to the size of the guest molecules; that is, it exactly depends on the carbon number of the alkylamines used for each reaction of poly(muconic acid) or poly(sorbic acid) crystals. The stacking structure of alkyl chains with a tilt in the intercalated alkylammonium layers exists irrespective of the chemical and crystal structures of the host polymers. The intercalation of higher alkylamines into poly(muconic acid) crystals proceeds fast and quantitatively, while the conversion is dependent on the reaction conditions such as the structure and amount of the amine and the reaction time during the intercalation with poly(sorbic acid) crystals, due to the difference in the repeating layered structures of these polymer crystals. Some functional amines are also used as the guest molecules for this organic intercalation system.     

三聚磷酸二氢铝与有机胺的插层反应特征

采用IR、XRD、SEM、EDS、DT-TG和滴定实验等技术手段研究主体三聚磷酸二氢铝(ATP)与客体甲胺、乙胺、正丙胺和正丁胺等有机胺的插层反应特性。 实验结果表明,ATP与甲胺、乙胺、正丙胺、正丁胺发生了化学反应,有机胺中的N与ATP层间-OH上的H形成配位键。 这些有机胺通过插层反应改变了ATP的酸性、层间距和热分解温度,但没有改变颗粒的层状形貌。 层间距从0.795 nm增大至1.71 nm,层间距d与有机胺的碳原子数Cn呈线性关系：d=0.229Cn+0.811,R2=0.9986。 有机胺分子链越长则越具有剥离倾向。     

新型超分子复合发光材料四足配体铕配合物-蒙脱土的插层组装及发光性质

通过离子交换反应将四足配体铕配合物[EuL(NO3)]2+[L=1,1,1’,1’-四(吡啶-2-羧酸酯基)联三甲基丙烷]插层组装到蒙脱土(MT)层板间, 制备出一种新型的超分子复合发光材料[EuL(NO3)]2+-MT. 用元素分析、XRD、FTIR、UV-Vis和热分析对材料进行了表征, 并对其荧光性质进行了研究. 结果表明, 复合材料保持了蒙脱土良好的层柱结构特征, 其层间距d(001)值与插层配离子的直径吻合得较好, 配离子以单层形式分布于蒙脱土层板间. 在紫外光激发下, 复合材料发出较强的Eu3+特征荧光, 其相对荧光强度、荧光单色性和荧光寿命大大优于相应配合物的乙醇溶液. 复合材料中配合物的发光性能、光稳定性和热稳定性较纯配合物有明显提高.     

Separation of nucleoside monophosphates using preferential anion exchange intercalation in layered double hydroxides

We report the first example of selective intercalation of nucleoside monophosphates in a layered host material. The intercalated nucleoside monophosphates can then be quantitatively recovered from the inorganic host and so this opens up the possibility of using simple layered inorganic hosts as rapid, cost effective and recyclable materials for the purification and separation of complex biomolecules.     

牛黄酸及水杨酸系药物对镁铝层状复合氢氧化物的插层组装

通过XRD和IR表征对镁铝层状复合氧氧化物(LDH)与水杨酸、乙酰氨基酚、乙酰水杨酸,以及谷氨酸、色氨酸、牛黄酸反应产物的比较分析,研究了不同药物对有关组装方式的适宜性.结果表明水杨酸类药物均可通过离子交换组装到LDH层间,晶胞参数c由2.3893 nm依次增大为2.4024、2.4110和2.4111nm,通道高度h由0.3194 nm增大为0.3238、0.3267和0.3268 nm;通过离子交换能将谷氨酸组装到LDH层间,产物的IR吸收、热分解行为及TEM形貌与前体有明显区别,晶胞参数c由2.3765nm增大为2.3851nm,h由0.3152nm增大为0.3180nm;共沉淀法适宜制备LDH-牛黄酸插层复合物,但简单的离子交换不能使色氨酸与LDH有效复合.     

Intercalative reaction of a cobalt(III) cage complex,Co(sep)3+, with magadiite,a layered sodium silicate

The cationic metal cage complex (1,3,6,8,10,13,16,19-octaazabicyclo[6.6.6]cicosane)cobalt(III), Co(sep)³⁺ has been investigated as a potential pillaring reagent for Na⁺-magadiite (Na_1.7Si₁₄O_27.9(OH)_1.9 · 7.6 H₂O) a synthetic layered sodium silicate. Reaction of Na⁺-magadiite with aqueous solutions of Co(sep)Cl₃ at 25°C resulted in the binding of Co(sep)³⁺ cations to the external crystalline surface of the layered silicate. In contrast, an intercalated product exhibiting a 17.6 Å basal spacing was generated by reaction at 100°C.²⁹Si MAS NMR and FT-IR spectroscopy indicate that Co(sep)³⁺ intercalated reaction products retain the magadiite layer structure. Moreover, scanning electron micrographs of the reaction products showed retention of the original particle morphology, suggesting a topotactic intercalation. However, during intercalation, some of the Co(sep)³⁺ was found to undergo an unusual demetalation reaction leaving a combination of Co(II) and Co(sep)³⁺ between the layers. Nitrogen surface area analysis showed that only a small amount of microporous surface existed in the Co(sep)³⁺ intercalated derivative, suggesting that most of the interlayer space is stuffed with cobalt species.     

Zn/V2O5水相二次电池的交流阻抗研究

The dependence of charge transfer resistances of electrodes in the aqueous Zn/V 2O 5 secondary battery on the Zn 2+ amount intercalated was studied by means of AC impedance experiments. The results showed that the electrode reaction on cathode was controlled by the diffusion of Zn 2+ at the beginning of the discharge process. With the increase of Zn 2+ amount intercalated into the cathode, the reaction became a kinetic controlled process, i.e.a process controlled by intercalation of Zn 2+ in V 2O 5.     

三氧化钼/苯胺层状复合材料的制备

以三氧化钼为无机主体, 用十二烷基胺对三氧化钼层间进行改性, 成功地制备了三氧化钼/苯胺层状复合材料. X射线衍射、元素分析、扫描电子显微镜、红外光谱测试及差热分析结果表明, 苯胺分子已成功地插入三氧化钼层间, 所得复合物化学式为[ANI]0.4MoO3. 插层后, 三氧化钼仍保持规则有序的层状结构, 其层间距扩大至1.318 nm. 讨论了无机主体与有机客体之间的相互作用、苯胺在层间的可能排布形式以及苯胺插入层间的反应机理.     

Solubility and release of fenbufen intercalated in Mg, Al and Mg, Al, Fe layered double hydroxides (LDH): The effect of Eudragit S 100 covering

Following different preparation routes, fenbufen has been intercalated in the interlayer space of layered double hydroxides with Mg²⁺ and Al³⁺ or Mg²⁺, Al³⁺ and Fe³⁺ in the layers. Well crystallized samples were obtained in most of the cases (intercalation was not observed by reconstruction of the MgAlFe matrix), with layer heights ranging between 16.1 and 18.8 Å. The presence of the LDH increases the solubility of fenbufen, especially when used as a matrix. The dissolution rate of the drug decreases when the drug is intercalated, and is even lower in those systems containing iron; release takes place through ionic exchange with phosphate anions from the solution. Preparation of microspheres with Eudragit^® S 100 leads to solids with an homogeneous, smooth surface with efficient covering of the LDH surface, as drug release was not observed at pH lower than 7.     

Nanocomposites of NLO chromophore‐modified layered silicates and polypropylene

Intercalation of guest species into layered inorganic solids is a method of producing ordered inorganic–organic assemblies with unique microstructures controlled by host–guest and guest–guest interactions. Smectite clay minerals, such as montmorillonite, having appropriate functional molecules in between the silicate layers are supposed to exhibit a wide range of novel characteristics. Nanocomposite material based on maleic anhydride‐grafted polypropylene and dye‐modified layered silicate was developed. Characteristics of organo‐modified montmorillonite particles and polymer/clay hybrids have been investigated through FTIR, SAXS, DSC, UV measurements, and transmission electron microscopy. The results of the intercalation process, structural characterization, and thermal properties will be discussed in comparison with the intercalation and nanocomposite preparation results. The intercalation was successfully conducted by the ion‐exchange method. It was shown that intercalated dibenzilidene acetone type chromophores exist in the clay galleries in an aggregated form, probably as J‐aggregates. This feature strongly effects on optical and nonlinear optical properties of nanocomposites. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 2493–2502, 2005     

Intercalation of dodecyl sulfate into layered double hydroxides

The intercalation of sodium dodecyl sulfate and exchange of dodecyl sulfate anion into layered double hydroxides has been examined by means of X-ray diffraction, infrared and thermogravimetric procedures. Three types of derivatives were obtained having mean interlayer spacings of 26 Å, 36 Å and 47 Å, respectively. These interlayer distances did not correlate with the amount of organic incorporated between the layers but, as shown by computer simulations, depended upon the orientation of the chains within the interlamellar space. In several reactions both intercalation of neutral sodium dodecyl sulfate as well as exchange of the dodecyl anion took place. Attempts to remove the alkyl sulfate chains with dilute acid resulted in dissolution of the more basic metals producing non-stoichiometric layered products.     

Intercalation of non-aromatic heterocyclic amines into layered zirconium glycine-<Emphasis Type="Italic">N,N</Emphasis>-dimethylphosphonate

New materials were prepared by intercalation reactions between layered zirconium glycine-N,N-dimethylphosphonate (ZGDMP) and non-aromatic heterocyclic amines: piperazine, piperidine, and morpholine. X-ray powder diffraction patterns showed that the entrance of piperazine, piperidine, and morpholine caused an interlayer expansion of 0.40 nm, 0.66 nm, and 0.67 nm, respectively. The infrared spectra were in agreement with an acid-base reaction, involving layered acid host COOH of ZGDMP and basic center atoms of guest molecules. Thermogravimetric curves revealed thermal stability of the intercalation compounds and content of the inserted amine molecules. These results indicate that non-aromatic heterocyclic amines were intercalated into the galleries of host ZGDMP.     

Intercalation of salicylic acid into ZnAl and MgAl layered double hydroxides for a controlled release formulation

Salicylic acid was intercalated into an inorganic host consisting of ZnAl/MgAl-layered double hydroxides lamella by reconstruction method. Powder X-ray diffractograms showed that the basal spacing of the layered double hydroxide bearing salicylate as the intergallery anion expanded from 7.6 and 7.8 Å in the precursors to 14.49 Å and 14.85 in ZnAl and MgAl layered double hydroxide, respectively. These values suggest that the organic molecules form bilayers in the interlayer space. Fourier transform infrared study further confirmed intercalation of salicylate into the interlayer’s of the layered double hydroxides. The thermal stability of the intercalated salicylic acid is significantly enhanced compared with the pure form before intercalation. Using the XRD results combined with a molecular simulation model, a possible representation of the salicylate anion positioning between the lamellar layers has been proposed. The in vitro drug release from intercalated material was remarkably lower than that from the corresponding physical mixture at pH 7.5. The kinetic analysis showed the importance of the diffusion through the particle in controlling the drug release rate. The obtained results show that hydrotalcite may be used to prepare modified release formulations.     

Synthesis and UV absorption properties of 2,3-dihydroxynaphthalene-6-sulfonate anion-intercalated Zn-Al layered double hydroxides

An organic UV absorbent has been intercalated into a layered double hydroxide (LDH) host by ion exchange of a Zn-Al-LDH-nitrate precursor with a solution of 2,3-dihydroxynaphthalene-6-sulfonic acid (DNSA) sodium salt in water. After intercalation of the UV absorbent, the powder X-ray diffraction (XRD) pattern shows that the interlayer distance in the LDHs increases from 0.90 to 1.59 nm. The possible structure is that the interlayer DNSA anions arrange in a monolayer and in a perpendicular orientation toward the hydroxide layers. Infrared spectra and TG-DTA curves reveal the presence of a complex system of supramolecular host-guest interactions between layers. The thermal stability of the intercalated UV absorbent was investigated by TG-DTA and it was found that this material is more stable than the original organic UV absorbent at high temperature, showing that the thermostability is markedly enhanced after intercalation into the LDH host. The UV absorbent-intercalated LDHs exhibit excellent UV photostability in polypropylene composites.     

Layered inorganic materials as redox agents: ferrocenium-intercalated zirconium phosphate

The direct intercalation reaction of ferrocene (bis(eta5-cyclopentadienyl)iron(II), Fc) with a highly hydrated layered zirconium phosphate (ZrP) resulted in the formation of the ferrocenium ion (Fc+) within the ZrP material. The Fc+-intercalated ZrP material has an interlayer distance of 10.7 A. The intercalated material was used as an electron acceptor for the oxidation of both ferro-cytochrome c and the excited state of tris(2,2'-bipyridine)ruthenium(II) ([Ru(bpy)3]2+). Upon contact of the material with a 1.5 x 10(-5) M solution of ferro-cytochrome c, the UV-vis absorption spectrum shows the successful formation of ferri-cytochrome c. Luminescence spectroscopy shows that the Fc+-intercalated ZrP material quenches the luminescence of [Ru(bpy)3]2+. The excited-state quenching mechanism of [Ru(bpy)3]2+* by Fc+-intercalated ZrP follows a dynamic plus sphere of action model. The second-order dynamic quenching rate constant kq is 2.2 x 10(8) M(-1) s(-1).