(392f) Gene Delivery Vehicles for Oral Inhalation Formulations

Pressurized metered-dose inhalers (pMDIs) are the least expensive oral inhalation devices for the regional delivery of small therapeutics to the lungs. More recently, pMDIs have received renewed attention as it has been demonstrated that inhalation therapy also holds promise for the delivery of therapeutic biomolecules including proteins, oligonucleotides, and peptides to and through (systemically) the lungs. However, most therapeutics (hydrophobic, hydrophilic and biomacromolecules) have very low solubility in the propellants used in pMDIs, typically requiring the formulation of drugs as suspensions. Another challenge arises when attempting to deliver nanotherapeutics to the lungs, as in the case of polymeric nanoparticles for gene delivery applications, as they can be efficiently exhaled due to their small size. In this work we describe a novel approach to formulate polymer-DNA nanoparticulates in propellant-based inhalers for gene delivery applications. The formulation of stable dispersions of the polymer-DNA complexes, their aerosol characteristics and transfection efficiency in lung epithelial cells are discussed. The relevance of this work stems from the fact that gene therapy is a promising approach to treat a variety of medically relevant diseases, including lung cancer and cystic fibrosis, and also due to the fact that pMDIs are the most widely used inhalation formulations in the market.