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J Control Release. 2019 Nov 25. pii: S0168-3659(19)30689-3. doi: 10.1016/j.jconrel.2019.11.030. [Epub ahead of print]

Feedback controlled photolytic gas phase nitric oxide delivery from S-nitrosothiol-doped silicone rubber films.

Author information

1
Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
2
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
3
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: mmeyerho@umich.edu.
4
Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: schwende@umich.edu.

Abstract

Constant therapeutic gas phase nitric oxide (NO) delivery is achieved from S-nitrosothiol (RSNO) type NO donor doped silicone rubber films using feedback-controlled photolysis. For photo-release of the NO gas, the intensity of the LED light source is controlled via a PID (proportional-integral-derivative) controller implemented on a microcontroller. The NO concentration within the emitted gas phase is monitored continuously with a commercial amperometric NO gas sensor. NO release was accurately adjustable up to 10 ppm across a broad range of setpoints with response times of roughly 1 min or less. When NO is generated into an air recipient stream, lower NO yields and a comparable level of toxic nitrogen dioxide (NO2) formation is observed. However, NO gas generated into an N2 recipient gas stream can be blended into pure O2 with very low NO2 formation. Following scale-up, this technology could be used for point-of-care gas phase NO generation as an alternative for currently used gas cylinder technology for treatment of health conditions where inhaled NO is beneficial, such as pulmonary hypertension, hypoxemia, and cystic fibrosis.

KEYWORDS:

Feedback control; Inhalation NO therapy; NO; Nitric oxide; S-nitrosothiol

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