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1.
J Vis Exp ; (108): 53248, 2016 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-26967828

RESUMO

This paper describes the synthesis and peroxide-modification of nanosize monosodium titanate (nMST), along with an ion-exchange reaction to load the material with Au(III) ions. The synthesis method was derived from a sol-gel process used to produce micron-sized monosodium titanate (MST), with several key modifications, including altering reagent concentrations, omitting a particle seed step, and introducing a non-ionic surfactant to facilitate control of particle formation and growth. The resultant nMST material exhibits spherical-shaped particle morphology with a monodisperse distribution of particle diameters in the range from 100 to 150 nm. The nMST material was found to have a Brunauer-Emmett-Teller (BET) surface area of 285 m(2)g(-1), which is more than an order of magnitude higher than the micron-sized MST. The isoelectric point of the nMST measured 3.34 pH units, which is a pH unit lower than that measured for the micron-size MST. The nMST material was found to serve as an effective ion exchanger under weakly acidic conditions for the preparation of an Au(III)-exchange nanotitanate. In addition, the formation of the corresponding peroxotitanate was demonstrated by reaction of the nMST with hydrogen peroxide.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Metais Alcalinos/química , Nanopartículas/química , Sódio/química , Titânio/química , Humanos , Tamanho da Partícula
2.
J Biomed Mater Res A ; 97(3): 348-54, 2011 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-21472975

RESUMO

Sodium titanates are ion-exchange materials that effectively bind a variety of metal ions over a wide pH range. Sodium titanates alone have no known adverse biological effects but metal-exchanged titanates (or metal titanates) can deliver metal ions to mammalian cells to alter cell processes in vitro. In this work, we test a hypothesis that metal-titanate compounds inhibit bacterial growth; demonstration of this principle is one prerequisite to developing metal-based, titanate-delivered antibacterial agents. Focusing initially on oral diseases, we exposed five species of oral bacteria to titanates for 24 h, with or without loading of Au(III), Pd(II), Pt(II), and Pt(IV), and measuring bacterial growth in planktonic assays through increases in optical density. In each experiment, bacterial growth was compared with control cultures of titanates or bacteria alone. We observed no suppression of bacterial growth by the sodium titanates alone, but significant (p < 0.05, two-sided t-tests) suppression was observed with metal-titanate compounds, particularly Au(III)-titanates, but with other metal titanates as well. Growth inhibition ranged from 15 to 100% depending on the metal ion and bacterial species involved. Furthermore, in specific cases, the titanates inhibited bacterial growth 5- to 375-fold versus metal ions alone, suggesting that titanates enhanced metal-bacteria interactions. This work supports further development of metal titanates as a novel class of antibacterials.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Portadores de Fármacos/química , Metais/administração & dosagem , Metais/farmacologia , Óxidos/química , Titânio/química , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico
3.
J Mater Sci Mater Med ; 21(4): 1289-95, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19941042

RESUMO

Amorphous peroxotitantes (APT) are insoluble titanium-based particles that bind a variety of metal compounds with high affinity; these particles could be sequestered locally in a solid phase to deliver metal-based drugs. Previous studies have confirmed the 'biodelivery' of metals from metal-APT complexes to fibroblasts, but not monocytes. Our goal in the current study was to use monocytic cytokine secretion to assess delivery of gold or platinum-based compounds from APT to human THP1 monocytes. Cytokine secretion was not triggered by APT alone or metal-APT complexes. In monocytes activated by lipopolysaccharide (LPS), APT alone enhanced or suppressed IL1beta or IL6 secretion, yet TNFalpha secretion was unaffected. Complexes of APT and Au(III) or cis-platin altered LPS-activated IL6 or IL1beta secretion most, TNFalpha least. Our results suggest that the APT deliver metals to monocytes.


Assuntos
Sistemas de Liberação de Medicamentos , Íons/farmacocinética , Metais/farmacocinética , Monócitos/metabolismo , Titânio/farmacocinética , Materiais Biocompatíveis/farmacocinética , Materiais Biocompatíveis/farmacologia , Células Cultivadas , Cisplatino/administração & dosagem , Cisplatino/farmacocinética , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Ouro/farmacocinética , Ouro/farmacologia , Humanos , Interleucina-6/metabolismo , Íons/administração & dosagem , Lipopolissacarídeos/farmacologia , Teste de Materiais , Metais/administração & dosagem , Monócitos/efeitos dos fármacos , Óxidos/farmacocinética , Óxidos/farmacologia , Titânio/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
4.
J Biomed Mater Res B Appl Biomater ; 91(2): 489-496, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19701912

RESUMO

Metal-based drugs are largely undeveloped in pharmacology. One limiting factor is the systemic toxicity of metal-based compounds. A solid-phase, sequestratable delivery agent for local delivery of metals could reduce systemic toxicity, facilitating new drug development in this nascent area. Amorphous peroxotitanates (APT) are ion-exchange materials with high affinity for several heavy metal ions and have been proposed to deliver or sequester metal ions in biological contexts. In the current study, we tested a hypothesis that APTs are able to deliver metals or metal compounds to cells. We exposed fibroblasts (L929) or monocytes (THP1) to metal-APT materials for 72 h in vitro and then measured cellular mitochondrial activity (SDH-MTT method) to assess the biological impact of the metal-APT materials versus metals or APT alone. APT alone did not significantly affect cellular mitochondrial activity, but all metal-APT materials suppressed the mitochondrial activity of fibroblasts (by 30-65% of controls). The concentration of metal-APT materials required to suppress cellular mitochondrial activity was below that required for metals alone, suggesting that simple extracellular release of the metals from the metal-APT materials was not the primary mechanism of mitochondrial suppression. In contrast to fibroblasts, no metal-APT material had a measurable effect on THP1 monocyte mitochondrial activity, despite potent suppression by metals alone. This latter result suggested that "biodelivery" by metal-APT materials may be cell type-specific. Therefore, it appears that APTs are plausible solid-phase delivery agents of metals or metal compounds to some types of cells for potential therapeutic effect.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Metais/administração & dosagem , Óxidos/química , Titânio/química , Linhagem Celular , Corantes , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Humanos , Metais/farmacologia , Metais/toxicidade , Metais Pesados/administração & dosagem , Metais Pesados/farmacologia , Metais Pesados/toxicidade , Mitocôndrias/efeitos dos fármacos , Succinato Desidrogenase/metabolismo , Sais de Tetrazólio , Tiazóis
5.
Inorg Chem ; 45(17): 6565-7, 2006 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-16903701

RESUMO

The anthracene lumiphore was linked to the chelating ligand 2,2'-bipyridine, forming 4-[N-(2-anthryl)carbamoyl]-4'-methyl-2,2'-bipyridine (bpyAnth). Coupling through an amide linkage provides some electronic isolation of the anthracene lumiphore. Electrochemistry suggested little change of the anthracene oxidation whether free (1.35 V) linked to 2,2'-bipyridine as bpyAnth (1.30 V) or appended to Fe(II) (1.29 V). The bpyAnth ligand retained the structured luminescence characteristic of anthracene at 375, 400, 419, and 441 nm. This anthracene emission persists even when bpyAnth is complexed to an Fe(II) center. The complex [Fe(bpyAnth)3]2+ is emissive, in marked contrast to typical polyazine iron(II) complexes. This bpyAnth ligand serves as a luminescently tagged analogue of 2,2'-bipyridine, useful for coordination to a variety of metals.

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