title: The efficacy of aerosol treatment with non-ionic surfactant vesicles containing amphotericin B in rodent models of leishmaniasis and pulmonary aspergillosis infection.
abstract: Amphotericin B (AMB) is used to treat both fungal and leishmanial infections, which are of major significance to human health. Clinical use of free AMB is limited by its nephrotoxicity, whereas liposomal AMB is costly and requires parenteral administration, thus development of novel formulations with enhanced efficacy, minimal toxicity and that can be applied via non-invasive routes is required. In this study we analysed the potential of non-ionic surfactant vesicles (NIV) given by nebulisation to deliver AMB to the lungs, liver and skin. Treatment with AMB-NIV resulted in significantly higher drug levels in the lungs and skin (p<0.05) compared to similar treatment with AMB solution but significantly lower plasma levels (p<0.05). Treatment with AMB-NIV resulted in a significant reduction in fungal lung burdens in a rat model of invasive pulmonary aspergillosis (p<0.05) compared to treatment with the carrier alone. Treatment with AMB-NIV but not AMB solution significantly suppressed Leishmania donovani liver parasite burdens (p<0.05) but could not inhibit the growth of cutaneous Leishmania major lesions. The results of this study indicate that aerosolised NIV enhanced pulmonary and hepatic delivery whilst minimising systemic exposure and toxicity.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, UK.
authors.forename: M
authors.initials: M
authors.lastname: Alsaadi
authors.forename: J L
authors.initials: JL
authors.lastname: Italia
authors.forename: A B
authors.initials: AB
authors.lastname: Mullen
authors.forename: M N V
authors.initials: MN
authors.lastname: Ravi Kumar
authors.forename: A A
authors.initials: AA
authors.lastname: Candlish
authors.forename: R A M
authors.initials: RA
authors.lastname: Williams
authors.forename: C D
authors.initials: CD
authors.lastname: Shaw
authors.forename: F
authors.initials: F
authors.lastname: Al Gawhari
authors.forename: G H
authors.initials: GH
authors.lastname: Coombs
authors.forename: M
authors.initials: M
authors.lastname: Wiese
authors.forename: A H
authors.initials: AH
authors.lastname: Thomson
authors.forename: M
authors.initials: M
authors.lastname: Puig-Sellart
authors.forename: J
authors.initials: J
authors.lastname: Wallace
authors.forename: A
authors.initials: A
authors.lastname: Sharp
authors.forename: L
authors.initials: L
authors.lastname: Wheeler
authors.forename: P
authors.initials: P
authors.lastname: Warn
authors.forename: K C
authors.initials: KC
authors.lastname: Carter
mesh_terms: D000336:Aerosols; D000666:Amphotericin B / Q000008:administration & dosage*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D006224:Cricetinae; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage*; D005260:Female; D049454:Firefly Luciferin / Q000008:administration & dosage; D007896:Leishmaniasis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D008099:Liver / Q000378:metabolism / Q000382:microbiology; D008168:Lung / Q000378:metabolism / Q000382:microbiology; D008647:Mesocricetus; D051379:Mice; D008807:Mice, Inbred BALB C; D055732:Pulmonary Aspergillosis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents / Q000008:administration & dosage*
chemical_list: D000336:Aerosols; D000935:Antifungal Agents; D004337:Drug Carriers; D013501:Surface-Active Agents; D049454:Firefly Luciferin; D000666:Amphotericin B