Aerosolized liposomal amphotericin B: Prediction of lung deposition, in vitro uptake and cytotoxicity
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- 作者：M¨¦lanie Fauvel ; C¨¦cile Farrugia ; Nicolas Tsapis ; Claire Gueutin ; Odile Cabaret ; Christian Bories ; St¨¦phane Bretagne ; Gillian Barratt
- 关键词：Liposomal amphotericin B ; A549 ; Nebulization ; MTT
- 刊名：International Journal of Pharmaceutics
- 出版年：2012
- 出版时间：15 October, 2012
- 年：2012
- 卷：436
- 期：1-2
- 页码：106-110
- 全文大小：279 K
文摘
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 ¦ÌM or more when 21.6 ¦Ìmoles 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 IC50 value of about 120 ¦ÌM after 24 h of exposure for D-AMB, but only a 13 % reduction in viability for 200 ¦ÌM 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.