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| An Analysis of SSH Ridges and SST Frontal Bands in Mid-Latitude Oceans | |
| 项目编号 | 1060397 |
| Peter Cornillon | |
| 项目主持机构 | University of Rhode Island |
| 开始日期 | 2011-04-15 |
| 结束日期 | 2015-09-30 |
| 英文摘要 | Our completed SBIR Phase I project (R43 DA031578) was in response to NIH PA11-096, PHS 2011-02 'Omnibus solicitation for SBIR/STTR Grant Application'under NIDA 2, "Development of Alternate Drug Delivery Dosage Forms for Drugs Abuse Studies." We have developed an alveolar region-targeted aerosol/inhalation method for nicotine delivery to rodents and developed devices with specialized software that enable this new method to be used effectively. In both the nose-only device and free-moving exposure chambers, the aerosol droplet size distribution is within the respirable diameter range. By physically imitating the properties of cigarette smoke, aerosol inhalation produces nicotine PK in both the arterial and venous blood resembling the PK profile of humans smoking cigarettes. This noninvasive method overcomes the limitations of current nicotine delivery methods. We have demonstrated that this novel method and device enable rapid delivery of a controllable amount of nicotine into systemic circulation and induces dose-dependent behavioral responses. The goal of this Phase II project is to translate the prototypes into commercialized products-"AeroDeliver(R)". Three Specific Aims are as follows: Aim 1. Develop and scale up a commercial product series of integrated aerosol inhalation systems including nose-only exposure devices and free-moving exposure chambers. We will create the integrated hardware and software, and scale up to simultaneously operate 16 AeroDeliver(R) systems. Aim 2. Further develop the novel alveolar region-targeted aerosol inhalation method for chronic intermittent nicotine exposure and validate it with animal testing. The device and protocol will be evaluated and validated using animal testing and by measuring plasma nicotine concentrations that simulate the PK profile in moderate to heavy human smokers. We will verify nicotine aerosol deposition in the lungs in vivo by positron emission tomography (PET) with radioactive labeled nicotine aerosol. Aim 3. Establish nicotine aerosol self-administration paradigms in drug dependence and reinforcement studies. The system will have positive and negative levers (for rats) or nosepoke sensors (for mice) for performance choice. The system will also perform fixed ratio (FR) and progressive ratio (PR) reinforcement schedules. We will evaluate the system in rodent experiments and compare the operation and results with conventional i.v. nicotine self-administration methods that use currently available commercial devices. In the course of animal testing, we will also develop an experimental "cookbook" with standardized protocols to facilitate comparison of results generated by different laboratories. Our products -AeroDeliver(R) system will be a powerful toolkit for studies of nicotine addiction, toxicology, teratogenicity and tobacco-related diseases, and ultimately, for facilitation of new therapeutic discovery. Furthermore, the significant potential for these toolkits to be used for other drugs of abuse such as marijuana, cocaine, and heroin will expand the market size for our products. |
| 英文关键词 | operation;Acute;Aerosols;Air;Air Pressure;Alveolar;Animal Model;Animal Testing;Animals;Applications Grants;Behavior;Behavioral;Blood;Blood Circulation;Breathing;Caliber;Cessation of life;Chronic;Cigarette;cigarette smoke;cigarette smoking;Circadian Rhythms;Cocaine;Computer software;Computers;Cookbook;Dependence;Deposition;desensitization;design;Detection;Development;Devices;disability;Disease;Dosage Forms;Dose;Drug Addiction;Drug Administration Routes;Drug Delivery Systems;Drug Kinetics;drug of abuse;Drug or chemical Tissue Distribution;drug reinforcement;Generations;Goals;Heroin;Human;Immobilization;in vivo;Infusion Pumps;Intake;Label;Laboratories;Light;Lung;Manuals;Marihuana;Marketing;Measures;meetings;Methods;Monitor;Mus;National Institute of Drug Abuse;Neurons;Nicotine;Nicotine Dependence;Nicotinic Receptors;Nose;novel;novel therapeutics;Oral;Performance;Pharmaceutical Preparations;Phase;Plasma;Play;Positron-Emission Tomography;Property;Protocols documentation;prototype;Psychological reinforcement;public health relevance;Radioactive;Rattus;Receptor Activation;Reinforcement Schedule;research study;response;Rodent;Role;scale up;Schedule;Seizures;Self Administration;sensor;Series;Simulate;Sleep;Small Business Innovation Research Grant;Small Business Technology Transfer Research;Smoker;Smoking;Smoking Behavior;software development;software systems;Subcutaneous Injections;System;Tail;Technology;Time;Tissues;Tobacco;Tobacco use;Toxic effect;Toxicology;Translating;Tremor;United States National Institutes of Health;vapor;Venous;Ventilatory Depression;Withdrawal |
| 学科分类 | 08 - 地球科学;0806 - 海洋科学 |
| 资助机构 | US-NSF |
| 项目经费 | 235428 |
| 项目类型 | Standard 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/75742 |
| 推荐引用方式 GB/T 7714 | Peter Cornillon.An Analysis of SSH Ridges and SST Frontal Bands in Mid-Latitude Oceans.2011. |
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