Complexation of Polyene Antibiotics with γ-Cyclodextrin

Abstract

γ-cyclodextrin inclusion complexes of 3 polyene antibiotics (Nystatin, Amphotericin B and Flavofungin) were prepared and examined in solid phase and in solution by solubility method, thermal analysis, X-ray diffractometry and spectroscopy. The solubility and dissolution rate of the studied polyenes were markedly increased by complexation. Acute toxicity test was performed on rats after s.c. administration of free and γ CD-complexed soluble Nystatin. Approximate LD₅₀ values and the serum levels indicate the improvement of absorption by at least one order of magnitude. Amphotericin-B even at physiological pH and salt concentration forms true solution — in the presence of sufficient high γcyclodextrin concentration, while solubilization with detergent type substances results only in colloidical dispersions. Stabilization of the very heat-sensitive Flavofungin against thermal degradation was succesful by complexation.