This is a health care and nanotechnology related research project. The lungs have been recently recognized as an attractive pathway to the bloodstream. Besides its noninvasive nature, aerosol inhalation therapies have several other advantages when compared to oral and parenteral approaches for the systemic delivery of therapeutics. The large absorptive area of the lungs and small aqueous volume that cover the lungs surface tend to favor rapid drug uptake. However, reduced concentrations of drug metabolizing enzymes (compared to those in the liver and gastrointestinal tract) help improve drug bioavailability. Aerosol inhalation therapy is also the most sensible route for the regional administration of therapeutics to the respiratory tract. Pressurized metered dose inhalers (pMDIs) are the most widely used devices for oral inhalation therapies due to their low cost, excellent compliance, and good aerosol characteristics. It is surprising (at least at first), therefore, that there are no commercial pMDI (or any other oral inhalation type) formulations for the systemic delivery of drugs, and important lung disease such as lung cancer and pulmonary tuberculosis are still being treated with i.v. and oral type formulations.
Intellectual Merit:
The lack of success in the development of propellant based aerosol formulations for treating such medically relevant diseases is related to our poor understanding on fundamental properties of HFAs such as solvation forces and difficulties in applying advanced/microscopic techniques to probe such systems under pressure. A basic understanding of how therapeutics interact with the lung epithelium, and their transport is also preventing the further development of aerosol formulations. In this work, the investigators address both issues (formulation development and lung therapeutic interactions). Propellant based aerosol formulations for the efficient delivery of nanoconstructs to and through the respiratory tract will be developed based on a combined computational and experimental approach. Systematic transport studies of candidate formulations containing the nanoconstructs will be investigated in model pulmonary epithelial membranes.
Broader Impacts:
Upon completion of this project, the investigators expect to develop novel pMDI formulations capable of efficiently delivering nanotherapeutics to and through the lungs. The research work will continue to be inclusive of undergraduates and area (Detroit) high school students, besides the involvement and training of graduate students. These opportunities are expected to enrich students and broadly impact the community. The privileged location of the Chemical Engineering Department at WSU allows the investigators to naturally outreach African American students, a largely underrepresented sector of the society in science and engineering. International collaboration and outreach with partners at institutions in South America will also continue.
