Abstract
The antimicrobial properties of nitric oxide (NO{filled circle}) have motivated the design of NO{filled circle}-releasing materials for the treatment and prevention of infection. The biological activity of NO{filled circle}is dependent on its delivery rate, suggesting that variable antimicrobial effects can result from identical NO{filled circle}payloads dosed at different rates. Using a kinetic model of the Escherichia coli NO{filled circle}biochemical network, we investigated the relationship between NO{filled circle}delivery rate, payload, and cytotoxicity, as indicated by the duration of respiratory inhibition. At low NO{filled circle}payloads, the model predicted greater toxicity with rapid delivery, while slower delivery was more effective at higher payloads. These predictions were conrmed experimentally, and exhibited quantitative agreement with measured O2 and NO{filled circle}concentrations, and durations of respiratory inhibition. These results provide important information on key design parameters in the formulation of NO{filled circle}-based therapeutics, and highlight the utility of a model-based approach for the analysis of dosing regimens.
Original language | English (US) |
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Pages (from-to) | 12-18 |
Number of pages | 7 |
Journal | Metabolic Engineering Communications |
Volume | 1 |
Issue number | 1 |
DOIs | |
State | Published - 2014 |
All Science Journal Classification (ASJC) codes
- Biomedical Engineering
- Endocrinology, Diabetes and Metabolism
Keywords
- Antimicrobial
- Escherichia coli
- Hmp
- Kinetic model
- Nitric oxide
- Nitric oxide dioxygenase
- Respiration