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1.
J Control Release ; 117(3): 312-21, 2007 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-17207879

RESUMO

A first feasibility study exploring the utility of poly(ethylene carbonate) (PEC) as coating material for drug eluting stents under in vitro conditions is reported. PEC (Mw 242 kDa, Mw/Mn=1.90) was found to be an amorphous polymer with thermoelastic properties. Tensile testing revealed a stress to strain failure of more than 600%. These properties are thought to be advantageous for expanding coated stents. In vitro cytotoxicity tests showed excellent cytocompatibility of PEC. Based on these findings, a new stenting concept was suggested, pre-coating a bare-metal stent with PPX-N as non-biodegradable basis and applying a secondary PEC coating using an airbrush method. After manual expansion, no delamination or destruction of the coating could be observed using scanning electron microscopy. The surface degradation-controlled release mechanism of PEC may provide the basis for "on demand" drug eluting stent coatings, releasing an incorporated drug predominantly at an inflamed implantation site upon direct contact with superoxide-releasing macrophages. As a release model, metal plates of a defined size and area were coated under the same conditions as the stents with PEC containing radiolabelled paclitaxel. An alkaline KO(2-) solution served as a superoxide source. Within 12 h, 100% of the incorporated paclitaxel was released, while only 20% of the drug was released in non-superoxide releasing control buffer within 3 weeks.


Assuntos
Materiais Biocompatíveis , Polietilenos/química , Stents , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Biotransformação , Varredura Diferencial de Calorimetria , Sobrevivência Celular/efeitos dos fármacos , Fenômenos Químicos , Físico-Química , Cromatografia em Gel , Elasticidade , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Camundongos , Microscopia Eletrônica de Varredura , Peso Molecular , Paclitaxel/administração & dosagem , Paclitaxel/farmacocinética , Paclitaxel/farmacologia , Resistência à Tração , Difração de Raios X
2.
Anal Chem ; 78(24): 8256-64, 2006 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-17165814

RESUMO

Atomic force microscopy and differential pulse voltammetry were used to characterize the interaction of small highly structured ribozymes with two carbon electrode surfaces. The ribozymes spontaneously self-assemble in two-dimensional networks that cover the entire HOPG surface uniformly. The full-length ribozyme was adsorbed to a lesser extent than a truncated RNA sequence, presumably due to the formation of a more compact overall structure. All four nucleobases composing the ribozyme could be detected by anodic voltammetry on glassy carbon electrodes, and no signals corresponding to free nucleobases were found, indicating the integrity of the ribozyme molecules. Mg2+ cations significantly reduced the adsorption of ribozymes to the surfaces, in agreement with the stabilization of this ribozyme's compact, stable, and tightly folded tertiary structure by Mg2+ ions that could prevent the hydrophobic bases from interacting with the HOPG surface. Treatment with Pb2+ ions, on the other hand, resulted in an increased adsorption of the RNA due to well-known hydrolytic cleavage. The observed dependence of anodic peak currents on different folding states of RNA may provide an attractive method to electrochemically monitor structural changes associated with RNA folding, binding, and catalysis.


Assuntos
Aptâmeros de Nucleotídeos , Carbono/química , RNA Catalítico/análise , RNA Catalítico/ultraestrutura , Absorção , Sequência de Bases , Sítios de Ligação , Catálise , Cátions Bivalentes , Eletroquímica/métodos , Eletrodos , Interações Hidrofóbicas e Hidrofílicas , Chumbo/química , Magnésio/química , Microscopia de Força Atômica/métodos , Conformação de Ácido Nucleico , RNA Catalítico/química
3.
Biochem Soc Trans ; 30(Pt 6): 1137-40, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12440990

RESUMO

Numerous RNA molecules with new catalytic properties have been isolated from synthetic combinatorial libraries. A broad range of chemical reactions is catalysed, and nucleic acids can accelerate bond formation between small organic substrates. This review focuses on carbon-carbon bond formation accelerated by in vitro selected ribozymes. Mechanistic investigations and structure-function relationships are discussed.


Assuntos
Carbono/química , RNA Catalítico/química , RNA/metabolismo , Sequência de Bases , Catálise , Modelos Químicos , Conformação de Ácido Nucleico , RNA/química
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