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1.
Pharmaceutics ; 12(8)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32752258

RESUMO

Bipyridinium salts, commonly known as viologens, are π-acceptor molecules that strongly interact with π-donor compounds, such as porphyrins or amino acids, leading their self-assembling. These properties have promoted us to functionalize polysilicon microparticles with bipyridinium salts for the encapsulation and release of π-donor compounds such as catecholamines and indolamines. In this work, the synthesis and characterization of four gemini-type amphiphilic bipyridinium salts (1·4PF6-4·4PF6), and their immobilization either non-covalently or covalently on polysilicon surfaces and microparticles have been achieved. More importantly, they act as hosts for the subsequent incorporation of π-donor neurotransmitters such as dopamine, serotonin, adrenaline or noradrenaline. Ultraviolet-visible absorption and fluorescence spectroscopies and high-performance liquid chromatography were used to detect the formation of the complex in solution. The immobilization of bipyridinium salts and neurotransmitter incorporation on polysilicon surfaces was corroborated by contact angle measurements. The reduction in the bipyridinium moiety and the subsequent release of the neurotransmitter was achieved using ascorbic acid, or Vitamin C, as a triggering agent. Quantification of neurotransmitter encapsulated and released from the microparticles was performed using high-performance liquid chromatography. The cytotoxicity and genotoxicity studies of the bipyridinium salt 1·4PF6, which was selected for the non-covalent functionalization of the microparticles, demonstrated its low toxicity in the mouse fibroblast cell line (3T3/NIH), the human liver carcinoma cell line (HepG2) and the human epithelial colorectal adenocarcinoma cell line (Caco-2).

2.
J Appl Toxicol ; 36(4): 510-20, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26708321

RESUMO

Tumor recurrence after the incomplete removal of a tumor mass inside brain tissue is the main reason that scientists are working to identify new strategies in brain oncologic therapy. In particular, in the treatment of the most malignant astrocytic tumor glioblastoma, the use of magnetic nanoparticles seems to be one of the most promising keys in overcoming this problem, namely by means of magnetic fluid hyperthermia (MFH) treatment. However, the major unknown issue related to the use of nanoparticles is their toxicological behavior when they are in contact with biological tissues. In the present study, we investigated the interaction of glioblastoma and other tumor cell lines with superparamagnetic iron-oxide nanoparticles covalently coated with a rhamnose derivative, using proper cytotoxic assays. In the present study, we focused our attention on different strategies of toxicity evaluation comparing different cytotoxicological approaches in order to identify the biological damages induced by the nanoparticles. The data show an intensive internalization process of rhamnose-coated iron oxide nanoparticles by the cells, suggesting that rhamnose moiety is a promising biocompatible coating in favoring cells' uptake. With regards to cytotoxicity, a 35% cell death at a maximum concentration, mainly as a result of mitochondrial damages, was found. This cytotoxic behavior, along with the high uptake ability, could facilitate the use of these rhamnose-coated iron-oxide nanoparticles for future MFH therapeutic treatments.


Assuntos
Carcinógenos/toxicidade , Materiais Revestidos Biocompatíveis/toxicidade , Dano ao DNA/efeitos dos fármacos , Dextranos/toxicidade , Nanopartículas de Magnetita/toxicidade , Ramnose/toxicidade , Animais , Carcinógenos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Dextranos/química , Glioblastoma/tratamento farmacológico , Humanos , Hipertermia Induzida , Nanopartículas de Magnetita/química , Camundongos , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo , Ramnose/química
3.
J Immunol Res ; 2014: 361419, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25032226

RESUMO

The attention on CeO2-NPs environmental and in vivo effects is due to their presence in diesel exhaust and in diesel filters that release a more water-soluble form of ceria NPs, as well as to their use for medical applications. In this work, acute and subacute in vivo toxicity assays demonstrate no lethal effect of these NPs. Anyhow, performing in vivo evaluations on CD-1 mouse systems, we demonstrate that it is even not correct to assert that ceria NPs are harmless for living systems as they can induce status of inflammation, revealed by hematological-chemical-clinical assays as well as histological and TEM microscope observations. TEM analysis showed the presence of NPs in alveolar macrophages. Histological evaluation demonstrated the NPs presence in lungs tissues and this can be explained by assuming their ability to go into the blood stream and lately into the organs (generating inflammation).


Assuntos
Cério/toxicidade , Inflamação/induzido quimicamente , Nanopartículas Metálicas/toxicidade , Animais , Análise Química do Sangue , Cério/administração & dosagem , Cério/química , Índices de Eritrócitos , Feminino , Inflamação/sangue , Inflamação/patologia , Rim/efeitos dos fármacos , Rim/patologia , Rim/ultraestrutura , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/ultraestrutura , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/ultraestrutura , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Macrófagos/ultraestrutura , Masculino , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Camundongos , Nódulos Linfáticos Agregados/efeitos dos fármacos , Nódulos Linfáticos Agregados/patologia , Testes de Toxicidade/métodos , Toxicologia
4.
J Nanosci Nanotechnol ; 12(8): 6185-91, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22962725

RESUMO

Safety and toxic effects of nanoparticles are still largely unexplored due to the multiple aspects that influence their behaviour toward biological systems. Here, we focus the attention on 12 nm spherical gold nanoparticle coated or not with hyaluronic acid compared to its precursor counterpart salt. Results ranging from the effects of a 10-days exposure in an in vitro model with BALB/c 3T3 fibroblast cells show how 12 nm spherical gold nanoparticles are internalized from 3T3 cells by endo-lysosomal pathway by an indirect measurement technique; and how gold nanoparticles, though not being a severe cytotoxicant, induce DNA damage probably through an indirect mechanism due to oxidative stress. While coating them with hyaluronic acid reduces gold nanoparticles cytotoxicity and slows their cell internalization. These results will be of great interest to medicine, since they indicate that gold nanoparticles (with or without coating) are suitable for therapeutic applications due to their tunable cell uptake and low toxicity.


Assuntos
Testes de Carcinogenicidade , Ouro/química , Nanopartículas Metálicas , Testes de Mutagenicidade , Células 3T3 , Animais , Dano ao DNA , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão
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