Controlled Photochemical Release of Nitric Oxide for Biomedical Applications
用于生物医学应用的一氧化氮的受控光化学释放
基本信息
- 批准号:10590662
- 负责人:
- 金额:$ 46.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-06-15 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:Acute Respiratory Distress SyndromeAdhesivesAffectAirAnimal TestingAnimalsAntiviral AgentsApicalBacteriaBiological AssayBloodBlood capillariesCell Culture TechniquesCell surfaceCellsChronicChronic Obstructive Pulmonary DiseaseClinicalCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDevicesDiseaseDissociationDoseElectron MicroscopyElectronicsEpithelial CellsExposure toFeedbackFilmFree RadicalsFrequenciesFundingGasesGenerationsGrantHistologyHomeHospitalsHumanIL8 geneIndividualInfectionInflammatoryIntensive CareIschemic Brain InjuryKnockout MiceLactate DehydrogenaseLightLightingLinkLungLung TransplantationLung infectionsMalariaMedicalMedicineMembraneMethemoglobinMethodsMicrobial BiofilmsModelingMonitorMorphologyMusMutationNeonatologyNitric OxideNitric Oxide DonorsNitrogen DioxideOrphan DrugsOutcomeOutputParticle SizePatientsPerformancePhasePneumoniaPolymersPopulationPorosityPrognosisPropertyPseudomonas aeruginosaPseudomonas aeruginosa infectionPulmonary HypertensionPulmonary TuberculosisReactionRegimenResearchResidual stateRespiratory Tract InfectionsRiskS phaseS-NitrosothiolsSignal TransductionSinusSinusitisSolidSputumStreamStrokeSurfaceSystemTechnologyTestingTherapeutic UsesTobramycinToxic effectVasodilator AgentsX ray diffraction analysisairway epitheliumantimicrobialantimicrobial drugcell preparationchronic rhinosinusitiscontrolled releasecostcrystallinitycystic fibrosis airway epitheliacystic fibrosis patientscytotoxichigh riskin vitro testingin-home careinfection riskinhaled nitric oxidelight intensitylight microscopylung failurenatural antimicrobialnovel strategiesparticleportabilitypressurepreventprototypescale upsensorsolid state
项目摘要
ABSTRACT: Therapeutic use of gas phase nitric oxide (NO) has several important applications in medicine. In
addition to its well-known vasodilator action, NO is a potent and endogenous antimicrobial agent normally
present at moderate levels (200-1000 ppbv) in the airways/sinuses of healthy individuals, which helps preventing
chronic upper airway and lung infections. Since its first medical application >20 years ago, inhaled nitric oxide
(iNO) has become a mainstay of intensive care for lung failure patients and it is essential in neonatology, lung
transplantation, and pulmonary hypertension. It is also used in pneumonia, acute respiratory distress syndrome
(ARDS), and potentially to treat of pulmonary tuberculosis and malaria. With the widespread hospital use of iNO
there is a great potential for use of iNO also in the home for treating chronic pulmonary infections related to
chronic obstructive pulmonary disease (COPD, ca. 11.5 million cases in US) and chronic rhino sinusitis (CRS,
ca. 31 million cases in US). Further, while cases of cystic fibrosis (CF) is less common (ca. 30,000 cases), CF
patients possess a genetic defect that greatly reduces NO levels liberated by airway epithelial cells, resulting in
very high risk of infection. However, iNO therapy is presently exceedingly expensive (>$3,000 per day) owing
to costly NO cylinders and the associated instability of NO in such gas tanks. Therefore, current NO delivery
technology is both too expensive and non-portable for potential routine use for in-home care.
Using funding from an exploratory R21 grant, our research team has developed a completely new and very
attractive method for light-activated NO generation directly from solid phase S-nitrosothiols (RSNO) type NO
donors. We have demonstrated that light-activated feedback-controlled release of NO can be achieved precisely
from RSNO loaded polymer films combined with variable LED lighting. An amperometric NO selective sensor
can provide signals for a feedback circuit to control the LED light intensity to achieve a target level of NO in the
output air (or O2) stream. We have identified the main parameters affecting the efficiency of NO release from
such films and for minimizing the emitted levels of toxic NO2 gas. In this R01 grant our team will further study
the possibilities of scaling up the light-activated NO generation system. We will test the purity of the generated
NO gas and the composition of the residual solid decomposition products in order to determine light triggered
reaction mechanism of the NO release from the solid state RSNO species. We will study the antimicrobial and
cytotoxic properties of the generated NO gas on bacteria infected human epithelial cells and in CFTR knockout
mice. This new photochemical gas phase NO generation approach will be very attractive and much lower in cost
than using current iNO delivery systems employing high pressure gas tanks. Indeed, photochemically generated
NO could eventually be safely extended to in-home use for certain clinical situations (e.g., CF, COPD, CRS and
ARDS) to prevent and treat chronic lung infections.
摘要:气相一氧化氮(NO)在医学上有几个重要的应用。在
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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STEVEN P. SCHWENDEMAN其他文献
STEVEN P. SCHWENDEMAN的其他文献
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{{ truncateString('STEVEN P. SCHWENDEMAN', 18)}}的其他基金
Controlled Photochemical Release of Nitric Oxide for Biomedical Applications
用于生物医学应用的一氧化氮的受控光化学释放
- 批准号:
10186743 - 财政年份:2020
- 资助金额:
$ 46.36万 - 项目类别:
Controlled Photochemical Release of Nitric Oxide for Biomedical Applications
用于生物医学应用的一氧化氮的受控光化学释放
- 批准号:
10377507 - 财政年份:2020
- 资助金额:
$ 46.36万 - 项目类别:
Controlled Photo-Release of Nitric Oxide for Antimicrobial Inhalation Therapy
用于抗菌吸入疗法的一氧化氮的受控光释放
- 批准号:
9298198 - 财政年份:2017
- 资助金额:
$ 46.36万 - 项目类别:
Investigation of peptide-polymer interactions in PLGA microspheres
PLGA 微球中肽-聚合物相互作用的研究
- 批准号:
9346576 - 财政年份:2016
- 资助金额:
$ 46.36万 - 项目类别:
In vitro-In vivo correlations of parenteral microsphere drug products
肠外微球药物产品的体外-体内相关性
- 批准号:
9131455 - 财政年份:2013
- 资助金额:
$ 46.36万 - 项目类别:
In vitro-In vivo correlations of parenteral microsphere drug products
肠外微球药物产品的体外-体内相关性
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8670377 - 财政年份:2013
- 资助金额:
$ 46.36万 - 项目类别:
Protein Stability in Polymer Delivery Systems
聚合物输送系统中的蛋白质稳定性
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7844194 - 财政年份:2009
- 资助金额:
$ 46.36万 - 项目类别:
Self-microencapsulation in polymer delivery systems without organic solvents
不含有机溶剂的聚合物输送系统中的自微囊化
- 批准号:
7739678 - 财政年份:2009
- 资助金额:
$ 46.36万 - 项目类别:
Self-microencapsulation in polymer delivery systems without organic solvents
不含有机溶剂的聚合物输送系统中的自微囊化
- 批准号:
7894812 - 财政年份:2009
- 资助金额:
$ 46.36万 - 项目类别:
Protein Stability in Polymer Delivery Systems
聚合物输送系统中的蛋白质稳定性
- 批准号:
6629146 - 财政年份:2001
- 资助金额:
$ 46.36万 - 项目类别:
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