Pharmacologically Safe Nanomicelles of Amphotericin B With Lipids: Nuclear Magnetic Resonance and Molecular Docking Approach

Abstract

This study presents the mode of interaction, structural features, and micellization of amphotericin B (AmB) with sodium deoxycholate sulfate (SDCS) as small lipid molecule at different ratios, as revealed by molecular docking simulations and nuclear magnetic resonance (NMR). AmB-SDCS micelles were synthesized by single pot rinsing method. Solid-state 13C NMR revealed hydrogen (H)-bonding as the main interaction, occurring at different positions between AmB and SDCS at various ratios. Molecular docking elucidated that AmB-SDCS complex was stabilized by multiple H-bonds and van der Waals forces between SDCS and AmB. SDCS molecules wrap around the AmB in a head-to-tail fashion into a nanomicellar structure. AmB-SDCS micelles were stable after freeze-drying and presented zeta potential values between −27.5 and −42.6 mV and particle size in the range of 63.9 to 203.1 nm, upon rehydration in water. Hematological toxicity of AmB was controlled by exposure versus release of drug from SDCS micelles and concentration of SDCS to envelop the drug. Hemolysis of human erythrocytes was significantly reduced as compared to market formulation Fungizone® and pure AmB. This study explained the chemical interaction of micellization of AmB in lipids, which can have greater implications in designing toxicologically safe formulations of hydrophobic drugs.