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1.
Anal Biochem ; 377(1): 33-9, 2008 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-18374654

RESUMEN

Enthalpy arrays enable label-free, solution-based calorimetric detection of molecular interactions in a 96-detector array format. The combination of the small size of the detectors and the ability to perform measurements in parallel results in a significant reduction of sample volume and measurement time compared with conventional calorimetry. We have made significant improvements in the technology by reducing the temperature noise of the detectors and improving the fabrication materials and methods. In combination with an automated measurement system, the advances in device performance and data analysis have allowed us to develop basic enzyme assays for substrate specificity and inhibitor activity. We have also performed a full titration of 18-crown-6 with barium chloride. These results point to future applications for enthalpy array technology, including fragment-based screening, secondary assays, and thermodynamic characterization of leads in drug discovery.


Asunto(s)
Calorimetría/métodos , Enzimas/metabolismo , Automatización/instrumentación , Compuestos de Bario/metabolismo , Calorimetría/instrumentación , Cloruros/metabolismo , Éteres Corona/metabolismo , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/farmacología , Hexoquinasa/metabolismo , Análisis por Matrices de Proteínas/instrumentación , Análisis por Matrices de Proteínas/métodos , Unión Proteica , Especificidad por Sustrato , Termodinámica , Volumetría , Inhibidores de Tripsina/metabolismo , Inhibidores de Tripsina/farmacología
2.
Hum Vaccin Immunother ; 11(8): 1936-44, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26090875

RESUMEN

We report a biolistic technology platform for physical delivery of particle formulations of drugs or vaccines using parallel arrays of microchannels, which generate highly collimated jets of particles with high spatial resolution. Our approach allows for effective delivery of therapeutics sequentially or concurrently (in mixture) at a specified target location or treatment area. We show this new platform enables the delivery of a broad range of particles with various densities and sizes into both in vitro and ex vivo skin models. Penetration depths of ∼1 mm have been achieved following a single ejection of 200 µg high-density gold particles, as well as 13.6 µg low-density polystyrene-based particles into gelatin-based skin simulants at 70 psi inlet gas pressure. Ejection of multiple shots at one treatment site enabled deeper penetration of ∼3 mm in vitro, and delivery of a higher dose of 1 mg gold particles at similar inlet gas pressure. We demonstrate that particle penetration depths can be optimized in vitro by adjusting the inlet pressure of the carrier gas, and dosing is controlled by drug reservoirs that hold precise quantities of the payload, which can be ejected continuously or in pulses. Future investigations include comparison between continuous versus pulsatile payload deliveries. We have successfully delivered plasmid DNA (pDNA)-coated gold particles (1.15 µm diameter) into ex vivo murine and porcine skin at low inlet pressures of ∼30 psi. Integrity analysis of these pDNA-coated gold particles confirmed the preservation of full-length pDNA after each particle preparation and jetting procedures. This technology platform provides distinct capabilities to effectively deliver a broad range of particle formulations into skin with specially designed high-speed microarray ejector nozzles.


Asunto(s)
Biolística/métodos , Sistemas de Liberación de Medicamentos/métodos , Sistemas Microelectromecánicos/métodos , Preparaciones Farmacéuticas/administración & dosificación , Polvos/administración & dosificación , Vacunas de ADN/administración & dosificación , Animales , Humanos , Ratones Endogámicos BALB C , Porcinos
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