Inhalation system for pulmonary aerosol drug delivery in rodents using large porous particles

The pulmonary system is an attractive noninvasive route for effective deliv ery of drugs for both local and systemic therapies. In this study, an inhal ation system was developed to effectively aerosolize and deliver small amou nts (typically 1-5 mg) of dry powder polymeric and nonpolymeric particles t o the lungs of anesthetized rodents over a very short period of time using a ventilator while the animals breathed spontaneously. The new aerosols wer e designed for size, porosity, and lightness and were characterized by part icles of low mass density (rho less than or equal to 0.1 g/cm(3)) and large size (d similar to 10 mu m). The inhalation system was tested in vivo to d etermine 1) whether the relatively efficient in vitro aerosolization of the se large porous particles translated into a substantial respirable fraction in vivo; 2) whether the bioavailability of an encapsulated drug for system ic therapy could be increased and the drug release in the systemic circulat ion could be sustained; and 3) whether an encapsulated drug for local asthm a therapy could sustain bronchodilation over a prolonged time period. Unlik e the conventional (small nonporous) particles which deposit primarily in t he tubing and trachea (80% of all particle mass delivered), 55% of the larg e porous particle mass deposited in the deep lung. The total systemic bioav ailabilities of inhaled porous estradiol, insulin, and testosterone relativ e to subcutaneous injections were 86%, 88%, and 177%, respectively. The inh aled dry powder albuterol sulfate aerosol was capable of preventing sustain ed bronchoconstriction tin response to carbachol challenge) for approximate ly one day. Our data indicate that the experimental inhalation system we de veloped will be an excellent device for further testing of new therapeutics available in particulate form.