LIPOSOMAL AEROSOLS IN THE MANAGEMENT OF PULMONARY INFECTIONS

The combination of liposomes and aerosols has been utilized to directl y target the Lungs with chemotherapeutic agents that might not have be en used because of low solubility or toxicity. There are a variety of antibacterials, antifungals, and antivirals that have good in vitro ac tivity, but are not effective because of their systemic toxicity and/o r poor penetration into the lungs. Incorporation of many lipophilic dr ugs into liposomes decreases their toxicity without affecting effectiv eness, thus increasing the therapeutic index. We have focused on aeros ol delivery of amphotericin B (ampB) for the treatment of pulmonary an d systemic fungal diseases. We have tested a variety of ampB-lipid for mulations for the optimal treatment regimen for Cryptococcus and Candi da infections in mouse models. The AeroTech II nebulizer (MMADs of 1.8 -2.2 mu m) produced aerosols with the highest concentrations in the br eathable range. Pharmacokinetic studies revealed that pulmonary drug w as present for hours to weeks. AmBisome retained its anticryptococcal activity even when animals were challenged 14 days after aerosol treat ment. Aerosols may also be effective in systemic diseases. In our Cand ida-mouse model, systemic candidiasis and mortality were reduced by ae rosolized ampB-liposome treatment. The ability to utilize lipophilic d rugs, to deliver high concentrations of drug directly to the site of i nfection, and to reduce toxicity makes aerosol liposomes an attractive , alternative route of administration.