RESUMO
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.
Assuntos
Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Ânions , Apoptose/efeitos dos fármacos , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Estabilidade de Medicamentos , Humanos , L-Lactato Desidrogenase/metabolismo , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Varredura , Nanotecnologia , Estresse Oxidativo/efeitos dos fármacosRESUMO
The increased applications of nanoparticles in a wide range of industrial fields raise the concern about their potential toxicity to human. The aim of this study was to assess and compare the toxicity of four different oxide nanoparticles (Al2O3, CeO2, TiO2 and ZnO) to human lung epithelial cells, A549 carcinoma cells and L-132 normal cells, in vitro. We focused on the toxicological effects of the present nanoparticles on cell proliferation, cell viability, membrane integrity and oxidative stress. The long-term cytotoxicity of nanoparticles was also evaluated by employing the clonogenic assay. Among four nanoparticles tested, ZnO exhibited the highest cytotoxicity in terms of cell proliferation, cell viability, membrane integrity and colony formation in both cell lines. Al2O3, CeO2 and TiO2 showed little adverse effects on cell proliferation and cell viability. However, TiO2 induced oxidative stress in a concentration- and time-dependent manner. CeO2 caused membrane damage and inhibited colony formation in long-term, but with different degree depending on cell lines. Al2O3 seems to be less toxic than the other nanoparticles even after long time exposure. These results highlight the need for caution during manufacturing process of nanomaterials as well as further investigation on the toxicity mechanism.
Assuntos
Óxido de Alumínio/toxicidade , Cério/toxicidade , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/fisiologia , Nanopartículas/toxicidade , Titânio/toxicidade , Óxido de Zinco/toxicidade , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/toxicidade , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Células Epiteliais/citologia , Humanos , Teste de MateriaisRESUMO
A most powerful antioxidant, glutathione (GSH), plays an important role in detoxification, immune response, and protection against reactive oxygen species. However, orally ingested GSH can be easily degradable to free amino acids by chemical and enzymatic hydrolysis, resulting in low bioavailability. The aim of this study was, therefore, to enhance GSH bioavailability by developing GSH-montmorillonite (MMT) hybrid system. It was also coated with polyvinylacetal diethylaminoacetate (AEA) for better stability. Both GSH-MMT and AEA-GSH-MMT hybrids were characterized by powder X-ray diffraction (PXRD), Fourier transformed infrared (FT-IR), and thermogravimetric analysis (TGA), indicating that GSH was successfully intercalated into the interlayer spaces of MMT. In vivo antioxidant activity assay revealed that AEA-GSH-MMT hybrid significantly increased antioxidant activity in the plasma after oral administration in mice. Pharmacokinetic study also indicated that AEA-GSH-MMT hybrid considerably increased the plasma concentration of GSH at 1h post-oral administration. Moreover, both the hybrid systems remarkably enhanced GSH delivery to the main target tissue, liver. All the results suggest that GSH-MMT hybrid systems have great potential to enhance bioavailability of oral GSH, providing new insight into their pharmaceutical application.
Assuntos
Antioxidantes/química , Bentonita/química , Portadores de Fármacos/química , Glutationa/química , Polivinil/química , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Bentonita/administração & dosagem , Bentonita/farmacocinética , Benzotiazóis/metabolismo , Disponibilidade Biológica , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacocinética , Estabilidade de Medicamentos , Glutationa/administração & dosagem , Glutationa/farmacocinética , Masculino , Camundongos , Camundongos Endogâmicos ICR , Polivinil/administração & dosagem , Polivinil/farmacocinética , Difração de Pó , Espectroscopia de Infravermelho com Transformada de Fourier , Ácidos Sulfônicos/metabolismo , Termogravimetria , Distribuição Tecidual , Difração de Raios XRESUMO
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.