In vivo anticancer activity of methotrexate-loaded layered double hydroxide nanoparticles.

A methotrexate (MTX)-loaded layered double hydroxide (LDH) nanoparticle system was synthesized by intercalating MTX into the interlayer spaces of LDH. In vivo pharmacokinetic study demonstrated that the MTX-LDH hybrid had similar kinetic behaviors as free MTX, showing a rapid decline in the plasma MTX level, with characteristics of a biexponential function. However, the hybrid system remarkably suppressed tumor growth in human osteosarcoma-bearing mice compared to an equivalent amount of free MTX. Using MTX-LDH nanoparticles, a significantly high amount of MTX was delivered to target tumor tissue, whereas a low level was found in normal tissues. Moreover, LDH nanocarriers did not accumulate in any specific tissue nor cause acute toxicity up to the applied dose for the hybrid system. These results suggest that the MTX-LDH nanohybrid system has great potential as an anti-cancer drug with enhanced in vivo anti-tumor activity and bioavailability in target tumor tissue along with reduced side effects.

Photoluminescent nanographitic/nitrogen-doped graphitic hollow shells as a potential candidate for biological applications.

Water-dispersible graphitic hollow spheres were synthesized using a soft chemical route under hydrothermal conditions by glucose carbonization using a magnetite/silica-encapsulated core-shell sphere as a template. Carbonization on the templates happens as the magnetite core is partially or completely eliminated depending on the reaction conditions. Therefore, nano-sized graphitic hollow spheres or magnetite-core-encapsulated graphitic shells could be obtained. Also nitrogen-doped graphitic spheres were synthesized by a hydrothermal reaction. The graphitic and nitrogen-doped graphitic spheres show wavelength dependent photoluminescence in 300-600 nm range. The photoluminescence seems to depend on the fraction of the sp2 domains and N-doping, therefore, tunable PL emission can be achieved by controlling the nature of sp2 sites. In addition the cellular uptake of the graphitic hollow spheres was evaluated in human HeLa cells, demonstrating its main localization in the cytoplasm. A blue fluorescence signal was the most intensively observed in the cellular uptake process, although some green and red fluorescence was also observed. Since the cores of Fe3O4 could be completely or partly eliminated in a controllable way, it can be used as a magnetic resonance imaging agent. In addition, their easily modifiable hydrophilic surfaces for multi-functionality and hydrophobic voids covered by oxidized graphite make them promising candidates for applications in cellular photo-imaging and 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.

Effect of different forms of anionic nanoclays on cytotoxicity.

Anionic nanoclays, so-called layered double hydroxide (LDH) nanoparticles, have been extensively applied as drug delivery systems, since they efficiently enter cells via endocytosis pathway and possess controlled release property. However, the stability of LDHs varies, depending on the type of interlayer anions, which can also affect their toxicity. In this study, we investigated the effects of two different forms of LDH, carbonate form (MgAl-LDH-CO3) and chloride form (MgAl-LDH-Cl), on cytotoxicity in human lung epithelial cells. The result showed that MgAl-LDH-Cl was more easily dissolved into metal ions under simulated lysosomal (pH 4.5) and body fluid (pH 7.4) conditions than did MgAl-LDH-CO3. According to cytotoxicity evaluation, MgAl-LDH-CO3 exhibited high toxicity compared with MgAl-LDH-Cl in terms of induction of oxidative stress, apoptosis and membrane damage. These results suggest that easily dissoluble MgAl-LDH-Cl has low cytotoxicity, while high stability of MgAl-LDH-CO3 is correlated to elevated cytotoxicity.