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| Micro-Electrocatalytic Upgrading of Carbon Dioxide to Hydrocarbons | |
| 项目编号 | DE-SC0015812 |
| Skinn, Brian | |
| 项目主持机构 | Faraday Technology, Inc. |
| 开始日期 | 2016-06-13 |
| 结束日期 | 2017-03-12 |
| 英文摘要 | Summary The lengthy treatment for tuberculosis (TB) is the primary cause of the emergence of multidrug resistant tuberculosis (MDR-TB), as it frequently results in non-compliance. Current chemotherapy for MDR-TB can last up to two years with multidrug regimens some of which are painful injectable drugs with serious associated toxicity. Eradication and control of TB depends on the development of shorter and more effective treatment regimens with minimal drug associated toxicity. One approach under study in this application is to develop an inhalational TB therapy [to replace injectable drugs] that when administered with oral TB drugs eases and shortens treatment. Aerosolized drug delivery unlike injectable agents is easy to administer and provides high pulmonary concentrations of antibiotics to the local site of infection thereby reducing the systemic level of exposure to the drug. A recently published article in Nature Medicine by the ?spectinamide consortium? showed that novel spectinamide analogs have excellent activity against Mycobacterium tuberculosis (Mtb) including MDR and XDR Mtb strains in vitro, as well as in vivo when administered by subcutaneous injection. In the same study, the lead compound spectinamide-1599 demonstrated strong efficacy against pulmonary TB when administered as a liquid formulation directly to the lungs of mice via intrapulmonary aerosol (IPA) delivery. By expanding on our preliminary data in this application Aim 1 will determine the pharmacokinetics (PK) and tissue distribution of spectinamide-1599 after IPA. Aim 2 will determine optimal dose, duration and frequency for treatment with spectinamide-1599 delivered by IPA and Aim3 will optimize a dry powder formulation of spectinamide-1599 to be used as inhalational TB therapy. These studies will be developed as a consortium between experts in the field of TB, inhalational animal models of TB and preclinical studies, pharmacokinetics and pharmacodynamics of TB chemotherapy and aerosol formulations and formulation of dry powders located at Colorado State University, University of Tennessee, Research Triangle Institute and St. Jude Children's Research Hospital. Working all together this consortium of researchers aims to advance research for this drug to the level that inhalational therapy via spectinamide-1599 can be considered a new drug/therapy candidate for TB. Thus, these studies will provide a formulation and inhalational therapy regimen of the spectinamide-1599 with well defined aerodynamic and PK properties and of well characterized in vivo efficacy for future testing in multidrug combination studies and in larger inhalational animal TB models and ultimately in TB patients. |
| 英文关键词 | Universities;tuberculosis treatment;tuberculosis drugs;Tuberculosis;Treatment Protocols;Toxic effect;Tissues;Time;therapy duration;Therapeutic;Testing;Tennessee;Subcutaneous Injections;subcutaneous;Site;s Research Hospital;Saint Jude Children'Safety;Route;response;Research Personnel;Research;Reporting;Regimen;Pulmonary Tuberculosis;Publishing;Property;Preclinical Testing;preclinical study;Powder dose form;Pharmacotherapy;Pharmacodynamics;Pharmaceutical Preparations;Performance;Patients;particle;Pain;Organ;Oral Tuberculosis;novel therapeutics;novel strategies;novel;non-compliance;Necrosis;Nature;Mycobacterium tuberculosis;Mus;Multidrug-Resistant Tuberculosis;Multi-Drug Resistance;Modeling;Medicine;Lung;Liquid substance;liquid formulation;Light;Length;Lead;Intravenous;Institutes;Injection of therapeutic agent;Injectable;Inhalators;Infection;Individual;Inbred BALB C Mice;in vivo;In Vitro;Hand;Granuloma;Goals;global health;Future;Frequencies;Formulation;Extreme drug resistant tuberculosis;extensive drug resistance;Exposure to;effective therapy;Drug-sensitive;Drug or chemical Tissue Distribution;Drug Kinetics;Drug Formulations;Drug Exposure;Drug Delivery Systems;drug candidate;Dose Fractionation;Dose;Disease;Devices;Development;Data;Critiques;Colorado;Clinical;Chronic;chemotherapy;Cavia;Breathing;Biological Availability;Antitubercular Antibiotics;Antitubercular Agents;Antibiotics;Anti-Bacterial Agents;Animals;Animal Model;analog;Aerosols;aerosolized;Aerosol Drug Therapy;Adverse effects |
| 学科分类 | 1103 - 工程热物理与能源利用;11 - 工程与技术;04 - 物理学 |
| 资助机构 | US-DOE |
| 项目经费 | 150000 |
| 项目类型 | Grant |
| 国家 | US |
| 语种 | 英语 |
| 文献类型 | 项目 |
| 条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/73819 |
| 推荐引用方式 GB/T 7714 | Skinn, Brian.Micro-Electrocatalytic Upgrading of Carbon Dioxide to Hydrocarbons.2016. |
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