A phospholipid–apolipoprotein A-I nanoparticle containing amphotericin B as a drug delivery platform with cell membrane protective properties

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• 作者：Braydon L. Burgess ; Giorgio Cavigiolio ; Michelle V. Fannucchi ; Beate Illek ; Trudy M. Forte ; Michael N. Oda
• 关键词：Nanodisk ; Amphotericin B ; Calu-3 cells ; HepG2 cells ; High density lipoprotein ; Lung epithelium ; Trans-epithelial K⁺ current ; Membrane protection ; Apolipoprotein A-I
• 刊名：International Journal of Pharmaceutics
• 出版年：2010
• 出版时间：31 October 2010
• 年：2010
• 卷：399
• 期：1-2
• 页码：148-155
• 全文大小：861 K

文摘

Amphotericin B (AMB), a potent antifungal agent, has been employed as an inhalable therapy for pulmonary fungal infections. We recently described a novel nano-sized delivery vehicle composed of phospholipid (PL) and apolipoprotein A-I, NanoDisk (ND), to which we added AMB as a payload (ND-AMB). The goal of the present study was to evaluate whether ND-AMB, compared to other formulations, preserves lung cell integrity in vitro, as AMB can be toxic to mammalian cells and reduce lung function when inhaled. Epithelial integrity was assessed by measuring K⁺ ion flux across a model airway epithelium, Calu-3 cells. In this assay ND-AMB was at least 8-fold less disruptive than AMB/deoxycholate (DOC). Cell viability studies confirmed this observation. Unexpectedly, the ND vehicle restored the integrity of a membrane compromised by prior exposure to AMB. An alternative formulation of ND-AMB containing a high load of AMB per ND was not protective, suggesting that ND with a low ratio of AMB to PL can sequester additional AMB from membranes. ND-AMB also protected HepG2 cells from the cytotoxicity of AMB, as determined by cellular viability and lactate dehydrogenase (LDH) levels. This study suggests that ND-AMB may be safe for administration via inhalation and reveals a unique activity whereby ND-AMB protects lung epithelial membranes from AMB toxicity.