The development of a biodegradable carrier to deliver antifungal agents at concentrations that inhibit microbial growth without altering osteoblast cell function

Fungal osteomyelitis is a rare and potentially life threatening condition. Current management involves the prolonged administration of antifungal agents and multiple surgical procedures. This study was designed to address the potential of developing an osteoconductive biodegradable carrier (BC) that can release therapeutic concentrations of antifungal agents. The hypothesis was to examine the sustained release of antifungal agents from loaded beta-tricalcium phosphate (TCP) BCs over six (6) weeks in concentrations that inhibit microbial growth, without altering the viability and function of osteoblast cells.;The research was conducted in four phases. Phase I was designed to determine the concentration of amphotericin B (AMB), fluconazole (FCZ), and micafungin (MFG) that would cause osteoblast cell damage. Phase II addressed the potential for increased rates of fungal osteomylelitis in immunocompromised patients and evaluated resultant osteoblast cell viability and function subsequent to co-administration of antifungal agents with cyclosporine. Phase III was designed to develop a BC capable of delivering therapeutic concentrations of antifungal agents. Phase IV was designed to test the delivery of the carrier in a tissue culture setting where osteoblast cells were preinoculated with C. albicans.;In phases I and II, cell proliferation, reduced glutathione, lipid membrane peroxidation, alkaline phosphatase activity, hematoxylin and eosin stains, and apoptosis were used to assess cell damage, function and viability. In phase III, beta-TCP BCs were cold compressed with antifungal agents and the concentration of elutants were determined spectrophotometrically. A standard bioassay was used to evaluate the activity of the eluted antifungal agent over six (6) weeks. Osteoblast cells were preinoculated with C. albicans, followed by treatment with antifungal BCs; and fungal colony formation was evaluated at 24,48 and 72 hours in phase IV.;Antifungal agents were released from beta-TCP BC in therapeutic concentrations without altering osteoblast growth and functional morphology. Overall, antifungal BCs may be used as efficient and safe options for treating fungal osteomyelitis in the clinical setting if these results are replicated in vivo.