(549e) A Trojan Horse Approach for the Non-Invasive Delivery of Nanotherapeutics to and through the Lungs

Inhalation therapy has been long utilized as an efficient route for the local (lung) delivery of therapeutics. More recently, it has been recognized as an efficient pathway to the systemic circulation. It has improved patient compliance, fast drug uptake - in the order of minutes or even seconds, and improved drug bioavailability. Inhalation therapy can also be used for the local and systemic delivery of therapeutic biomolecules. Nanotechnology offers great promise in combination with inhalation therapies. Nanoparticles can be used as efficient carriers of nucleotides and other therapeutic biomolecules. Nanoparticles can also be designed so as to target specific cell organelles or for the controlled release of therapeutics. However, a suitable formulation is required in order to deliver very small particles to the lungs. The optimal aerosol size for lung deposition lies between ~0.4 ? 5 μm, larger particles being deposited in the mouth/throat, while smaller particles may be exhaled. In this work we will discuss a novel propellant-based inhalation formulation that can be used to efficiently deliver nanoparticles to the deep lungs. We show that biodegradable and biocompatible core-shell particles with solute-laden nanoparticles may be effectively dispersed in hydrofluoroalkane propellants, generating aerosols with enhanced characteristics. The applicability of the technology is demonstrated in vitro by investigating the ability of the nanoparticles in the core-shell formulation to reach the inclusions of chlamydial-infected lung epithelial cells.