The majority of AIDS patients, when first examined, have symptoms of opportunistic infections, the most common being Pneumocystis carinii. The high mortality rate defines a need for treatment and prophylaxis of this and other life-threatening opportunistic infections. Pentamidine has a role to play, but, issues associated with its delivery by inhalation still exist. The objective of this project is to improve inhalation therapy of microbial infections secondary to AIDS. Feasibility will be demonstrated in Phase I using previously developed fine particle suspensions. Concurrently pentamidine-free-base particle suspensions will be developed for use in Phase II comparison with current formulations in controlled animal studies. These pentamidine studies will test the hypothesis that ultrafine particle dispersions, which behave very much like true solutions, can improve inhalation therapy of microbial infections. Additional Phase II objectives will be to apply the ultrafine particle dispersion technology to other anti-crobials, including experimental antiviral, agents. The technology developed in this project also should be useful for the delivery of other pharmaceuticals, e.g., poorly soluble steroids and sustained release formulations of mast cell stabilizers to the lung periphery. Systemic delivery of peptides and other pharmaceuticals may also be improved by knowledge acquired in this project.
