Micelles self-assembled from poly(ethylene oxide)-block-poly(N-hexyl stearate L-aspartamide) by a solvent evaporation method:: effect on the solubilization and haemolytic activity of amphotericin B

The goal of this study was to assess a solvent evaporation method for the encapsulation of amphotericin B (AmB) in poly(ethylene oxide)-block-poly(N-hexyl stearate L-aspartamide) (PEO-b-PHSA) micelles. By the solvent evaporation method, PEO-b-PHSA self-assembled into small spherical micelles with a high AmB content based on transmission electron microscopy, size exclusion chromatography and absorption spectroscopy. The encapsulation of AmB was slightly better than an earlier method based on dialysis. Importantly, AmB in PEO-b-PHSA micelles encapsulated by the solvent evaporation method was non-haemolytic at 15 mug/ml, whereas AmB in PEO-b-PHSA micelles encapsulated by the dialysis method caused 50% haemolysis at the level of 3.8 mug/ml, and AmB itself caused 100% haemolysis at 1.0 mug/ml. Thus, PEO-b-PHSA micelles could effectively encapsulate AmB, increase the overall water solubility of AmB and reduce the toxicity of the membrane-acting drug, particularly by a solvent evaporation method. (C) 2001 Elsevier Science B.V. All rights reserved.