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Merck

Evaluation of two sources of calcium sulfate for a local drug delivery system: a pilot study.

Clinical orthopaedics and related research (2011-05-10)
Ashley C Parker, J Keaton Smith, Harry S Courtney, Warren O Haggard
RESUMEN

Local drug delivery has substantial potential to prevent infections compared with systemic delivery. Although calcium sulfate (CaSO(4)) has been studied for local drug delivery and two types are commercially available, it is unknown whether they differentially release antibiotics. We determined the differences between two sources of CaSO(4) and the K(2)SO(4) catalyst's presence on the degradation, daptomycin elution, and activity against Staphylococcus aureus. We formed pellets from synthetic and naturally sourced (from gypsum) CaSO(4) and loaded with 5% daptomycin and 3% or 0% K(2)SO(4). We used in vitro experiments to determine the daptomycin concentration and degradation profiles over 10 days. Turbidity assays were used to evaluate the activity of the daptomycin eluates against S. aureus. All pellets exhibited a bolus release with the highest daptomycin concentration on Day 1 with the sourced CaSO(4) pellets. The synthetic CaSO(4) pellets with 3% K(2)SO(4) exhibited a slower drug release compared with the synthetic CaSO(4) pellets with 0% K(2)SO(4), which degraded and eluted daptomycin too quickly to inhibit S. aureus. Turbidity assays demonstrated that all CaSO(4) pellets inhibit S. aureus for expected lengths of time. Our preliminary in vitro data suggest differences in the degradation, elution, and activity properties between sourced and synthetic CaSO(4) pellets. The addition of K(2)SO(4) appeared beneficial when using synthetic CaSO(4). Synthetic CaSO(4) may be effective when slow degradation and longer elution times are needed. Local delivery of eluted daptomycin can be tailored through material selection and K(2)SO(4) addition.

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