Hydrophobized poly(vinyl alcohol) for encapsulation of amphotericin B in nanoparticles

Amphotericin B (AmB) is a broad-spectrum fungicidal antibiotic used primarily in the treatment of life-threatening systemic fungal infections. Since AmB is sparingly soluble in water, we have attempted to render it soluble and transportable by encapsulating it in poly(vinyl alcohol) (PVA) nanoparticles. The formation of monodisperse nanoparticles by self-assembly of the hydrophobized PVA and their complex formation with AmB was studied by size-exclusion chromatography and dynamic light scattering. AmB encapsulated in the PVA nanoparticle was non-hemolytic, even at 100 μg/mL, whereas Fungizone (AmB-desoxycholate) at 10 μg/mL caused 50 % hemolysis. The biodistribution of both AmB-loaded PVA nanoparticles and AmBisome (liposomal AmB) in mice was compared. After intravenous injection of the AmB-loaded PVA nanoparticles, prolonged persistence of AmB in the blood circulation, as well as a low hepatic distribution, was observed.