RESUMO
The synthesis, material characterization, and in vitro biocompatibility of S-nitrosothiol (RSNO)-modified xerogels are described. Thiol-functionalized xerogel films were formed by hydrolysis and co-condensation of 3-mercaptopropyltrimethoxysilane (MPTMS) and methyltrimethoxysilane (MTMOS) sol-gel precursors at varying concentrations. Subsequent thiol nitrosation via acidified nitrite produced RSNO-modified xerogels capable of generating nitric oxide (NO) for up to 2 weeks under physiological conditions. Xerogels also exhibited NO generation upon irradiation with broad-spectrum light or exposure to copper, with NO fluxes proportional to wattage and concentration, respectively. Xerogels were capable of storing up to approximately 1.31 micromol NO mg(-1), and displayed negligible fragmentation over a 2-week period. Platelet and bacterial adhesion to nitrosated films was reduced compared to non-nitrosated controls, confirming the antithrombotic and antibacterial properties of the NO-releasing materials. Fibroblast cell viability was maintained on the xerogel surfaces illustrating the promise of RSNO-modified xerogels as biomedical device coatings.
Assuntos
Géis/metabolismo , Óxido Nítrico/metabolismo , S-Nitrosotióis/metabolismo , Animais , Antibacterianos/farmacologia , Antitrombinas/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Plaquetas/ultraestrutura , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Compostos de Organossilício , Ativação Plaquetária/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Silanos/metabolismo , Sus scrofaRESUMO
Xerogel sensing films were synthesized via sol-gel chemistry were used to fabricate optical nitroxyl (HNO) sensors [corrected] Selective detection of HNO in solution was achieved by monitoring the rates of manganese(III) meso-tetrakis(4-sulfonatophenyl) porphyrinate (MnIIITPPS) reductive nitrosylation in the anaerobic interior of aminoalkoxysilane-derived xerogel films. Nitroxyl permeability in sensor films deposited in round-bottom 96-well plates was enhanced via incorporation of trimethoxysilyl-terminated poly(amidoamine-organosilicon) dendrimers in the xerogel network. The selectivity of MnIIITPPS for HNO, the overall sensitivity, and the working dynamic range of the resulting sensors were characterized. The HNO-sensing microtiter plates were used to quantify pH-dependent HNO generation by the recently described HNO-donor sodium 1-(isopropylamino)diazene-1-ium-1,2-diolate (IPA/NO), and compare HNO production efficiency between IPA/NO and Angeli's salt, a traditional HNO-donor.
Assuntos
Técnicas Biossensoriais/métodos , Géis/química , Óxidos de Nitrogênio/análise , Óptica e Fotônica , Dióxido de Silício/química , Concentração de Íons de Hidrogênio , Cinética , Manganês/química , Fármacos Neuroprotetores/análise , Compostos Organometálicos/química , Compostos de Organossilício/química , Porfirinas/química , Sensibilidade e EspecificidadeRESUMO
A xerogel-based optical pH sensor capable of releasing low levels of nitric oxide (NO) and measuring changes in solution pH is reported. Through simple dip-coating procedures, aminoalkoxysilane-based xerogel films modified with N-diazeniumdiolate NO donor precursors and the fluorescent pH indicator seminaphthorhodamine-1 carboxylate (SNARF-1) were sequentially deposited onto optical fibers. The resulting sensors were characterized by fast and linear response to pH throughout the physiological range (pH 7.0-7.8). Real-time chemiluminescence measurements confirmed that the presence of the overlying SNARF-1-containing TMOS layer did not have an inhibitory effect on N-diazeniumdiolate formation or NO release, and the NO-releasing coatings were capable of maintaining NO fluxes >0.4 pmol/cm(2) s up to 16 h. In vitro blood compatibility studies using porcine platelets confirmed the expected thromboresistivity of the NO-releasing xerogel coatings.
Assuntos
Tecnologia de Fibra Óptica , Concentração de Íons de Hidrogênio , Óxido Nítrico/química , Animais , Benzopiranos/química , Plaquetas/citologia , Plaquetas/ultraestrutura , Adesão Celular , Corantes Fluorescentes/química , Géis , Microscopia Eletrônica de Varredura , Naftóis/química , Fibras Ópticas , Reprodutibilidade dos Testes , Rodaminas/química , Sensibilidade e Especificidade , SuínosRESUMO
Nitric oxide (NO)-releasing xerogel membranes were prepared as coatings for an electrochemical glucose biosensor to allow for enhanced biocompatibility while maintaining adequate response times and sensitivity. Formation of the NO-donor species was found to drastically decrease the permeability of the aminosilane-based xerogels to both hydrogen peroxide and glucose. The addition of poly(vinylpyrrolidone) (PVP) polymer enhanced the membrane permeability even after exposure to high pressures of NO (necessary for NO-donor synthesis). The analytical response and NO release of PVP-doped NO-releasing xerogels as glucose sensor membranes were further investigated and found to be enhanced via polymer doping. Doping of the polymer into the xerogel did not compromise the stability of the xerogel as evaluated by silicon leaching studies. Despite the addition of PVP, the NO-releasing xerogels maintained reduced bacterial adhesion characteristics analogous to previous reports for NO-releasing xerogels.