Abstract
Kollicoat IR (KOL) is a new poly(ethylene glycol)-poly(vinyl alcohol) graft copolymer that is a promising material for medical applications because of its biocompatibility and hydrophilic nature. Amphotericin B (AmB) is a broad-spectrum fungicidal antibiotic used primarily in the treatment of life-threatening systemic fungal infections. However, AmB is limited in clinical use because of its poor water solubility. In this study, we synthesized AmB-loaded hydrophobized KOL nanoparticles for the first time. These self-assembled, stable nanoparticles exhibited a high AmB content. Among the hydrophobized KOL nanoparticles, a cholesterol-grafted KOL nanoparticle reduced AmB toxicity with respect to hemolysis and effectively increased the overall water solubility of AmB. Furthermore, a relatively high retention of AmB in the plasma was demonstrated in vivo in an animal experiment at early time after injection, suggesting that the cholesterol-grafted KOL nanoparticles could enable new pharmaceutical applications for AmB.
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