Inhalation System for Pulmonary Aerosol Drug Delivery in Rodents Using Large Porous Particles

The pulmonary system is an attractive noninvasive route for effective delivery of drugs for both local and systemic therapies. In this study, an inhalation system was developed to effectively aerosolize and deliver small amounts (typically 1-5 mg) of dry powder polymeric and nonpolymeric particles to the lungs of anesthetized rodents over a very short period of time using a ventilator while the animals breathed spontaneously. The new aerosols were designed for size, porosity, and lightness and were characterized by particles of low mass density (rho less than or equal to 0.1 g/cm3) and large size (d approximately 10 mum). The inhalation system was tested in vivo to determine 1) whether the relatively efficient in vitro aerosolization of these large porous particles translated into a substantial respirable fraction in vivo; 2) whether the bioavailability of an encapsulated drug for systemic therapy could be increased and the drug release in the systemic circulation could be sustained; and 3) whether an enc...