Analytical Sciences

Lipid Membrane-Binding Properties of Amphotericin B Deoxycholate (Fungizone) Using Surface Plasmon Resonance

Masako OKA and Hiroshi KAMIMORI

Pharmaceutical Research Division, Shionogi & Co., Ltd., 3-1-1 Futaba, Toyonaka, Osaka 561-0825, Japan

In the present study, we developed an assay of interactions of amphotericin B (AmB) deoxycholate, Fungizone, with two model lipid membranes that mimicked mammal cell membranes and fungal membranes. We also analyzed the binding kinetics of the mammal cell membranes and fungal membranes using surface plasmon resonance (SPR). Fungizone showed a higher affinity for the model fungal membrane than that of the model mammal cell membrane, and the binding selectivity of Fungizone in the temperature dependence could be represented by this SPR system. This method also showed reproducible immobilization of model liposome membranes on the sensor chip under two temperature conditions (25 and 37°C). The binding characteristics of the medicinal additive of Fungizone, sodium deoxycholate, were clarified on the assay of interactions of the drug product to the lipid membrane, and it was confirmed that the sodium deoxycholate did not affect the estimation of membrane selectivity of Fungizone. Furthermore, the affinities of AmB and Fungizone were discussed by comparing these affinity constants. The results demonstrate that this newly established SPR method could be applied to estimate the lipid-membrane interaction of Fungizone as a drug product of AmB.

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