(276h) Nanocarriers for Pressurized Metered-Dose Inhalers: Formulation, Aerosol Performance, and in-Vitro Transport Studies

Oral inhalation is a promising alternative to traditional routes of administration for the regional (lung) and systemic delivery of therapeutics. Even greater opportunities may lie ahead if recent advances in nanomedicine can be translated to such non-invasive delivery routes. Despite recent advances in the formulation of both small molecules and therapeutic biomolecules for pulmonary delivery, our knowledge of the interaction of these inhaled formulations with the lung is very limited. The formulation of nanotherapeutics in the propellants used in pressurized metered-dose inhalers (pMDIs) is also very challenging, given the size range required for optimum deep lung deposition ? particles smaller than 0.5 μm may be efficiently exhaled, while those larger than 4 μm will be deposited preferentially in the mouth and throat.

In this work we discuss the formulation of a general platform for the delivery of nanocarriers (NCs) to the lungs using pMDIs. The physical stability (in the propellant) and the aerosol performance of the NC-based formulations will be discussed, as well as the fundamentals leading to the ability to generate stable dispersions in pMDIs. The interaction of the NCs with a model lung epithelial membrane in vitro, and the transport of solutes across the epithelial barrier will be also discussed.

Key Words: metered-dose inhalers, pMDIs, oral inhalation, nanocarriers, in vitro cellular transport, nanocarrier cell interaction.