Model-driven identification of dosing regimens that maximize the antimicrobial activity of nitric oxide.
Metab Eng Commun
; 1: 12-18, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-34150500
ABSTRACT
The antimicrobial properties of nitric oxide (NOâ) have motivated the design of NOâ-releasing materials for the treatment and prevention of infection. The biological activity of NOâ is dependent on its delivery rate, suggesting that variable antimicrobial effects can result from identical NOâ payloads dosed at different rates. Using a kinetic model of the Escherichia coli NOâ biochemical network, we investigated the relationship between NOâ delivery rate, payload, and cytotoxicity, as indicated by the duration of respiratory inhibition. At low NOâ payloads, the model predicted greater toxicity with rapid delivery, while slower delivery was more effective at higher payloads. These predictions were confirmed experimentally, and exhibited quantitative agreement with measured O2 and NOâ concentrations, and durations of respiratory inhibition. These results provide important information on key design parameters in the formulation of NOâ-based therapeutics, and highlight the utility of a model-based approach for the analysis of dosing regimens.
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Base de dados:
MEDLINE
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article