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.
We are developing an alveolar region-targeted aerosol/inhalation method and devices for nicotine delivery to rodents. Aerosol inhalation produces nicotine concentrations in the blood resembling human smoking cigarettes. Our products -AeroDeliver(R) system is a powerful toolkit for studies of nicotine addiction, toxicology, teratogenicity and tobacco-related diseases, and ultimately, for facilitating discovery of new therapeutics.
| Shao, Xuesi M; López-Valdés, Héctor E; Liang, Jing et al. (2017) Inhaled nicotine equivalent to cigarette smoking disrupts systemic and uterine hemodynamics and induces cardiac arrhythmia in pregnant rats. Sci Rep 7:16974 |
| Xie, Xinmin Simon (2015) The neuronal circuit between nociceptin/orphanin FQ and hypocretins/orexins coordinately modulates stress-induced analgesia and anxiety-related behavior. Vitam Horm 97:295-321 |
| Shao, Xuesi M; Xu, Bin; Liang, Jing et al. (2013) Nicotine delivery to rats via lung alveolar region-targeted aerosol technology produces blood pharmacokinetics resembling human smoking. Nicotine Tob Res 15:1248-58 |
| Vazquez-DeRose, Jacqueline; Stauber, Gregory; Khroyan, Taline V et al. (2013) Retrodialysis of N/OFQ into the nucleus accumbens shell blocks cocaine-induced increases in extracellular dopamine and locomotor activity. Eur J Pharmacol 699:200-6 |
