Liposomal aerosols in the management of pulmonary infections.
The combination of liposomes and aerosols has been utilized to directly target the lungs with chemotherapeutic agents that might not have been used because of low solubility or toxicity. There are a variety of antibacterials, antifungals, and antivirals that have good in vitro activity, but are not effective because of their systemic toxicity and/or poor penetration into the lungs. Incorporation of many lipophilic drugs into liposomes decreases their toxicity without affecting effectiveness, thus increasing the therapeutic index. We have focused on aerosol delivery of amphotericin B (ampB) for the treatment of pulmonary and systemic fungal diseases. We have tested a variety of ampB-lipid formulations for the optimal treatment regimen for Cryptococcus and Candida infections in mouse models. The AeroTech II nebulizer (MMADs of 1.8-2.2 microns) produced aerosols with the highest concentrations in the breathable range. Pharmacokinetic studies revealed that pulmonary drug was present for hours to weeks. AmBisome retained its anticryptococcal activity even when animals were challenged 14 days after aerosol treatment. Aerosols may also be effective in systemic diseases. In our Candida-mouse model, systemic candidiasis and mortality were reduced by aerosolized ampB-liposome treatment. The ability to utilize lipophilic drugs, to deliver high concentrations of drug directly to the site of infection, and to reduce toxicity makes aerosol liposomes an attractive, alternative route of administration.
Gilbert
B E
BE
Department of Microbiology and Immunology, Baylor College of Medicine, Houston Texas 77030, USA.
D000336:Aerosols / Q000627:therapeutic use*; D000666:Amphotericin B / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008081:Liposomes; D008172:Lung Diseases, Fungal / Q000188:drug therapy*; D051379:Mice; D018410:Pneumonia, Bacterial / Q000188:drug therapy*; D011024:Pneumonia, Viral / Q000188:drug therapy*