Water-in-Hydrofluoroalkane Reverse Microemulsions for Pressurized Metered Dose Inhalers: Novel Delivery Vehicles for Hydrophilic Drugs Including Peptides, Proteins and DNA (CTS:0553537)
Intellectual Merit. Aerosol inhalation therapy offers several advantages over oral and parenteral approaches for the systemic delivery of drugs. Pressurized metered dose inhalers (pMDIs) are the least expensive aerosol therapy devices available, accounting for approximately 80 % of the total prescribed aerosols. They generate worldwide sales in excess of $ 2 billion per year. pMDI-based formulations are, therefore, potential candidates for the delivery of pharmaceutically relevant biomolecules including peptides, proteins and DNA. The development of novel pMDI-based formulations for the delivery of hydrophilic substances has been challenged, however, by the replacement of CFCs with the more environmentally friendly hydrofluoroalkanes (HFAs). In spite of the fact that the operation of pMDIs with HFAs is similar to those with CFCs, previous formulations are not compatible due to the significantly different properties between these two classes of fluids. Difficulties in studying the fundamental interfacial properties of volatile propellants has hindered the design of novel HFA-based formulations. Lack of such fundamental knowledge prevents extension of the applicability of pMDIs for the delivery of drugs to treat medically important diseases. In this work, the PI proposes to rationally design surfactants capable of forming and stabilizing biomolecule-containing aqueous reverse microemulsions in HFA propellants, using a combined computer simulation and experimental approach.
Broader Impacts. Several merit criteria are addressed in this proposal. Upon completion of this project, it is expected that one might develop HFAbased pMDI formulations capable of delivering biomolecules and other hydrophilic drugs to and through the lungs, for the treatment of diseases including diabetes, cancer, and cystic fibrosis. Research efforts will actively involve graduate, undergraduate, as well as high-school students, through active participation in research activities in our laboratories and outreach / partnership with institutions abroad. The PI will continue to provide research opportunities in their laboratories to students from the Detroit Public Schools through the High-School Student Apprentice Program.