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  • Title: Aerosolized liposomal amphotericin B: prediction of lung deposition, in vitro uptake and cytotoxicity.
    Author: Fauvel M, Farrugia C, Tsapis N, Gueutin C, Cabaret O, Bories C, Bretagne S, Barratt G.
    Journal: Int J Pharm; 2012 Oct 15; 436(1-2):106-10. PubMed ID: 22814222.
    Abstract:
    To predict the efficacy and toxicity of pulmonary administration of liposomal amphotericin B (L-AMB) for the treatment or the prevention of pulmonary invasive aspergillosis, a multistage liquid impinger was used to estimate the concentrations of drug that could be attained in different lung compartments after nebulization. The highest concentration of amphotericin B was found in the alveolar compartment, where it was calculated that the concentration in the lung surfactant could reach 54 μM or more when 21.6 μmoles of drug as liposomes was nebulized. The uptake and toxicity of L-AMB were studied in vitro using the A549 human lung epithelial cell line. Uptake was time and concentration-dependent and reached intracellular concentrations exceeding the minimal inhibitory concentrations for most Aspergillus species. The toxicity of L-AMB toward these cells, estimated by the MTT reduction assay, was reduced compared with the conventional form, deoxycholate amphotericin B (D-AMB), with an IC(50) value of about 120 μM after 24 h of exposure for D-AMB, but only a 13% reduction in viability for 200 μM L-AMB at 24 h. These results indicate that aerosol therapy with nebulized L-AMB could be efficient but that doses need to be carefully controlled to avoid toxicity.
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