Resorbable Beads Provide Extended Release of Antifungal Medication: In Vitro and In Vivo Analyses

Abstract

Fungal osteomyelitis has been difficult to treat, with first-line treatments consisting of implant excision, radical debridement, and local release of high-dose antifungal agents. Locally impregnated antifungal beads are another popular treatment option. This study aimed to develop biodegradable antifungal-agent-loaded Poly(d,l-lactide-co-glycolide) (PLGA) beads and evaluate the in vitro/in vivo release patterns of amphotericin B and fluconazole from the beads. Beads of different sizes were formed using a compression-molding method, and their morphology was evaluated via scanning electron microscopy. Intrabead incorporation of antifungal agents was evaluated via Fourier-transform infrared spectroscopy, and in vitro fluconazole liberation curves of PLGA beads were inspected via high-performance liquid chromatography. When we implanted the drug-incorporated beads into the bone cavity of rabbits, we found that a high level of fluconazole (beyond the minimum therapeutic concentration [MTC]) was released for more than 49 d in vivo. Our results indicate that compression-molded PLGA/fluconazole beads have potential applications in treating bone infections.

Keywords

• fluconazole
• orthopedic infection
• d,l-lactide-co-glycolide) beads%22%2C%22default_operator%22%3A%22AND%22%7D%7D%7D"> poly(<span style="font-variant: small-caps">d</span>,<span style="font-variant: small-caps">l</span>-lactide-<i>co</i>-glycolide) beads
• sustained release