Self-Assembled Teicoplanin Micelles as Amphotericin B Nanocarrier

Abstract

Teicoplanin (Teico) is an antimicrobial agent that spontaneously forms micelles in aqueous media. In this work, we characterized the physicochemical properties of nanoparticles formed by the interaction of Teico with Amphotericin B (AmB). Teico-AmB micelles structure spontaneously in aqueous media, with a particle size of 70–100 nm and a zeta potential of -28 mV. Although the characterization of these nanostructures yielded satisfactory results, in vitro cytotoxicity tests showed high toxicity. Based on this, adding cholesterol to the formulation was evaluated to try to reduce the toxicity of the drug. These Teico-AmB-Chol nanostructures have a larger size, close to 160 nm, but a lower polydispersity index. They also showed strongly negative surface charge and were more stable than Teico-AmB, remaining stable for at least 20 days at 4 °C and 25 °C and against centrifugation, dilution, freezing, lyophilization and re-suspension processes with a recovery percentage of AmB greater than 95%, maintaining their initial size and zeta potential. These Teico-AmB-Chol micelles show lower cytotoxic effect and higher biological activity than Teico-AmB, even than Amfostat® and Ambisome® formulations. These two new nanoparticles, with and without Chol, are discussed as potential formulations able to improve the antifungal therapeutic efficiency of AmB.