Nicotine delivery to rodent with lung alveolar region-targeted aerosol technology

Information

  • Research Project
  • 8525015
  • ApplicationId
    8525015
  • Core Project Number
    R44DA031578
  • Full Project Number
    2R44DA031578-02
  • Serial Number
    031578
  • FOA Number
    PA-12-088
  • Sub Project Id
  • Project Start Date
    4/1/2011 - 13 years ago
  • Project End Date
    5/31/2015 - 9 years ago
  • Program Officer Name
    SINGH, HARI
  • Budget Start Date
    6/1/2013 - 11 years ago
  • Budget End Date
    5/31/2014 - 10 years ago
  • Fiscal Year
    2013
  • Support Year
    02
  • Suffix
  • Award Notice Date
    5/1/2013 - 11 years ago
Organizations

Nicotine delivery to rodent with lung alveolar region-targeted aerosol technology

DESCRIPTION (provided by applicant): 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.

IC Name
NATIONAL INSTITUTE ON DRUG ABUSE
  • Activity
    R44
  • Administering IC
    DA
  • Application Type
    2
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    506122
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    279
  • Ed Inst. Type
  • Funding ICs
    NIDA:506122\
  • Funding Mechanism
    SBIR-STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    AFASCI, INC.
  • Organization Department
  • Organization DUNS
    160127655
  • Organization City
    REDWOOD CITY
  • Organization State
    CA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    940633848
  • Organization District
    UNITED STATES