Bioactivity and toxicity studies of amphotericin B incorporated in liquid crystals

The main objective of the present work was to evaluate the bioactivity and safety of amphotericin B–liquid crystal mixtures (AmB–LC). The effects of liquid crystal (LC) materials and AmB–LC ratios on bioactivity and toxicity to respiratory cell lines were investigated. The formation of AmB–LC mixtures did not change the physical properties of LC when the AmB loading was not more than a 1:3 mole ratio (25%). The exposure of respiratory cell lines to LC did not generate any toxicity (2.5–80 μg/mL). The inhibitory activity of AmB in all liquid crystal formulations (cholesteryl palmityl carbonate: CPC, dicholesteryl carbonate: DCC and sodium cholesteryl carbonate: SCC) on fungi was significantly enhanced when compared to that of the same amount of pure AmB. However, their toxicity to respiratory related cells and red blood cells was significantly decreased. This could be a huge advantage in clinical applications as there is more possibility for dose adjustments. The exposure of small airway epithelial cells (SAEC) and alveolar macrophages (AMs NR8383) to liquid crystals had no significant detrimental effects at doses of between 2.5 and 80 μg/mL (viability was always over 80%). The production of toxic cytokines and inflammatory mediators, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and nitric oxide (NO), after treatment with AmB in liquid crystals at concentrations of between 2 and 32 μg/mL was significantly reduced by about a 1000-fold compared to that generated by lipopolysaccharide (LPS).

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