Jin-Ho Choy

The effect of synthetic conditions on tailoring the size of hydrotalcite particles

Abstract The hydrotalcite particles of Mg 2 Al(OH) 6 (CO 3 ) 1/2 ·0.1H 2 O have been prepared by two different methods: (1) direct coprecipitation of aqueous solution of Mg(NO 3 ) 2 ·6H 2 O, Al(NO 3 ) 3 ·9H 2 O upon hydrolysis of urea, and (2) hydrothermal aging of the same nitrate solution after NaOH titration. In order to control the particle size and morphology of hydrotalcite, various parameters such as metal ion concentration, aging time, reaction temperature are systematically studied. According to the powder X-ray diffraction, all the samples turn out to be well crystallized with an average basal spacing of 7.6 A corresponding to the hydrotalcite crystal. From the SEM images, the coprecipitates are found to be hexagonal in shape and are controlled in the particle size range of 0.9–2.2 and 1.2–4.5 μm depending on aging time (6–69 h) and metal ion concentration (0.87–0.065 M), respectively. However, the particle size of the hydrothermally prepared samples increase in proportion to aging time (12–72 h ; 85–120 nm) and reaction temperature (100–180 °C; 115–340 nm). The effect of such parameters upon the particle size was rationalized on the basis of crystal growth mechanism.

Toxicological effects of inorganic nanoparticles on human lung cancer A549 cells

Many researches have shown that anionic clays can be used as delivery carriers for drug or gene molecules due to their efficient cellular uptake in vitro, and enhanced permeability and retention effect in vivo. It is, therefore, highly required to establish a guideline on their potential toxicity for practical applications. The toxicity of anionic clay, layered metal hydroxide nanoparticle, was evaluated in two human lung epithelial cells, carcinoma A549 cells and normal L-132 cells, and compared with that in other human cancer cell lines such as cervical adenocarcinoma cells (HeLa) and osteosarcoma cells (HOS). The present nanoparticles showed little cytotoxic effects on the proliferation and viability of four cell lines tested at the concentrations used (<250 microg/ml) within 48 h. However, exposing cancer cells to high concentrations (250-500 microg/ml) for 72 h resulted in an inflammatory response with oxidative stress and membrane damage, which varied with the cell type (A549>HOS>HeLa). On the other hand, the toxicity mechanism seems to be different from that of other inorganic nanoparticles frequently studied for biological and medicinal applications such as iron oxide, silica, and single walled carbon nanotubes. Iron oxide caused cell death associated with membrane damage, while single walled carbon nanotube induced oxidative stress followed by apoptosis. Silica triggered an inflammation response without causing considerable cell death for both cancer cells and normal cells, whereas layered metal hydroxide nanoparticle did not show any cytotoxic effects on normal L-132 cells in terms of inflammation response, oxidative stress, and membrane damage at the concentration of less than 250 microg/ml. It is , therefore, highly expected that the present nanoparticle can be used as a efficient vehicle for drug delivery and cancer cell targeting as well.

Controlled release of donepezil intercalated in smectite clays.

The inorganic-organic hybrid for a drug delivery system was successfully realized by intercalating donepezil molecules into smectite clays (laponite XLG, saponite, and montmorillonite). According to the powder XRD patterns, TG profiles, and FT-IR spectra, it was confirmed that donepezil molecules were well stabilized in the interlayer space of clay via mono or double layer stacking. The adsorption amount and molecular structure of donepezil appeared to depend on the cation exchange capacity of the clay, which in turn, tailored the drug release patterns. Especially in the presence of a bulky cationic polymer (Eudragit E-100) in the release media, the release rate was found to be improved due to its effective replacement with intercalated donepezil molecules. Therefore, to formulate a complete drug delivery system, the hybrids were coated with Eudragit E-100 using a spray dryer, which also showed great enhancement in the release rate during a short period of time (180min).

Layered nanomaterials for green materials

In this feature article, the applications of layered nanomaterials as green materials are demonstrated along with their structures and properties. Due to the unique 2-dimensional structures and biocompatibility, various eco- and bio-friendly materials can be hybridized with layered nanoparticles such as layered double hydroxides (LDHs), hydroxy double salts (HDSs) and cationic clays. From small molecules such as drugs, herbicides, fertilizers, and food ingredients to large substances like deoxyribonucelotides (DNA), protein, and enzymes, various functional materials can be incorporated into layered nanoparticles via intercalation reactions to produce green materials with versatile applications. The application fields of layered nanomaterials, especially LDHs, are summarized into three categories; biomolecule reservoir, pharmaceutical and other applications.

Bio-LDH nanohybrid for gene therapy

Abstract Nano-sized inorganic clay, such as layered double hydroxide (LDH), has been demonstrated as delivery carrier for genes and drugs by hybridizing with DNA and c-antisense oligonucleotide (As- myc ). Upon intercalating biomolecules into hydroxide layers, the basal spacing of LDH increases from 8.7 A (for NO 3 − ) to 23.9 A (DNA) and 17.1 A (As- myc ), respectively. A strong suppression of cell growth (65%) is observed when the HL-60 cells are incubated with 20 μM As- myc –LDH hybrid. However, LDH itself is found to be noncytotoxic on HL-60 cells (leukemia cells). Based on these findings, it is proved that LDHs can act as a new inorganic carrier which is completely different from ever existing nonviral vectors in terms of its chemical bonding and structure.

Inorganic Metal Hydroxide Nanoparticles for Targeted Cellular Uptake Through Clathrin-Mediated Endocytosis

Layered double hydroxides (LDHs) are biocompatible materials which can be used as drug-delivery nanovehicles. In order to define the optimum size of LDH nanoparticles for efficient cellular uptake and drug-delivery pathway, we prepared different sized LDH nanoparticles with narrow size distribution by modulating the crystal growth rate, and labelled each LDH particle with a fluorophore using a silane coupling reaction. The cellular uptake rate of LDHs was found to be highly dependent on particle size (50 > 200 > or = 100 > 350 nm), whose range of 50 to 200 nm was selectively internalized into cells through clathrin-mediated endocytosis with enhanced permeability and retention. Our study clearly shows that not only the particle size plays an important role in the endocytic pathway and processing, but also the size control of LDH nanoparticles results in their targeted uptake to site-specific clathrin-mediated endocytosis. This result provides a new perspective for the design of LDH nanoparticles with maximum ability towards targeted drug delivery.

Pharmacokinetics, tissue distribution, and excretion of zinc oxide nanoparticles

Background This study explored the pharmacokinetics, tissue distribution, and excretion profile of zinc oxide (ZnO) nanoparticles with respect to their particle size in rats. Methods Two ZnO nanoparticles of different size (20 nm and 70 nm) were orally administered to male and female rats, respectively. The area under the plasma concentration-time curve, tissue distribution, excretion, and the fate of the nanoparticles in organs were analyzed. Results The plasma zinc concentration of both sizes of ZnO nanoparticles increased during the 24 hours after administration in a dose-dependent manner. They were mainly distributed to organs such as the liver, lung, and kidney within 72 hours without any significant difference being found according to particle size or rat gender. Elimination kinetics showed that a small amount of ZnO nanoparticles was excreted via the urine, while most of nanoparticles were excreted via the feces. Transmission electron microscopy and x-ray absorption spectroscopy studies in the tissues showed no noticeable ZnO nanoparticles, while new Zn-S bonds were observed in tissues. Conclusion ZnO nanoparticles of different size were not easily absorbed into the bloodstream via the gastrointestinal tract after a single oral dose. The liver, lung, and kidney could be possible target organs for accumulation and toxicity of ZnO nanoparticles was independent of particle size or gender. ZnO nanoparticles appear to be absorbed in the organs in an ionic form rather than in a particulate form due to newly formed Zn-S bonds. The nanoparticles were mainly excreted via the feces, and smaller particles were cleared more rapidly than the larger ones. ZnO nanoparticles at a concentration below 300 mg/kg were distributed in tissues and excreted within 24 hours. These findings provide crucial information on possible acute and chronic toxicity of ZnO nanoparticles in potential target organs.

Human-related application and nanotoxicology of inorganic particles: complementary aspects

In this highlight, the emerging new discipline of nanotoxicology is discussed in terms of nanomedicine, nanocosmetics, and nanofood. In particular, a wide variety of applications of inorganic layered double hydroxide (LDH) nanoparticles in multidisciplinary fields and their potential toxicity compared to that of other inorganic nanoparticlesin vitro as well as in vivo are described in detail. Study on the toxicity of nanoparticles can provide critical information about their practical biological applications, finally contributing to the sustainable development of nanotechnology with safe and biocompatible levels.

A novel synthetic route to TiO2-pillared layered titanate with enhanced photocatalytic activity

A novel pillaring procedure has been developed to prepare TiO2-pillared layered titanate with large surface area, high thermal stability, and enhanced photocatalytic activity.

Layered double hydroxide nanoparticles as target-specific delivery carriers: uptake mechanism and toxicity

Layered double hydroxides (LDHs), also known as anionic nanoclays or hydrotalcite-like compounds, have attracted a great deal of interest for their potential as delivery carriers. In this article, we describe the cellular uptake behaviors and uptake pathway of LDHs in vitro and in vivo, which can not only explain the mechanism by which high efficacy of biomolecules delivered through LDH nanocarriers could be obtained, but also provide novel strategies to enhance their delivery efficiency. Toxicological effects of LDHs in cell lines and in animal models are also present, aiming at providing critical information about their toxicity potential, which should be carefully considered for their biomedical application. Understanding the uptake behaviors, uptake mechanism and toxicity of LDHs in terms of dose-response relationship, diverse physicochemical properties and interaction with different biological systems is important to optimize delivery efficiency as well as biocompatibility.