The majority of AIDS patients, at some point in their clinical course, 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 problems exist with its inhalation delivery. The objective of this project is to improve inhalation therapy of microbial infections secondary to AIDS. Feasibility was demonstrated in Phase I using previously developed fine particle suspensions. Pentamidine particle suspensions will be used in Phase Il comparison with current formulations in controlled animal studies to test the hypothesis that fine particle dispersions, which behave much like solutions, can improve inhalation therapy of microbial infections. Phase II objectives include testing regional lung deposition and clearance of particles as well as prophylaxis and therapy in the ferret model for PCP using pentamidine particle suspensions in comparison with the standard, water-soluble, isethionate formulation. The technology developed in this project should improve therapy of PCP with inhaled pentamidine and should be useful for delivery of other pharmaceuticals, e.g., poorly soluble anticancer and antifungal drugs, to the lung periphery. Systemic delivery of peptides and other pharmaceuticals may also be improved by knowledge acquired in this project.
