CarboCell G/C provides sustained high local bone antibiotic levels with minimal systemic exposure, supporting its therapeutic potential in orthopedic infection management

Abstract. Introduction: Achieving sustained local antibiotic concentrations is critical for managing orthopedic infections. This proof-of-concept study evaluated release kinetics, local/systemic concentrations, and histological responses to CarboCell G/C, an injectable gentamicin- and clindamycin-eluting depot in a porcine bone void model. Methods: CarboCell G/C containing 111 mg g−1 gentamicin-docusate and 70 mg g−1 clindamycin was injected into and around a tibial bone void in 11 pigs. Antibiotic concentrations in target tissues and systemic spillover were measured at 1–12 h by microdialysis and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) and in tissue homogenates at 1, 3, and 7 d. Release was quantified by high-performance liquid chromatography (HPLC), and tolerability was assessed histologically. Results: Microdialysis showed high stable antibiotic tissue levels during the first 12 h with minimal systemic spillover. Peak gentamicin and clindamycin concentrations in bone were 730 ± 170 and 3700 ± 700 µg g−1 and 42 ± 15 and 360 ± 120 µg g−1 in soft tissue, respectively. Tissue half-lives ranged from 43–62 h for clindamycin and 40–46 h for gentamicin. Recovered depots had released ∼ 30 %–50 % of their antibiotic content at day 1 and ∼ 60 %–80 % by day 7. Depots elicited a mild–moderate local inflammatory response. Conclusion: CarboCell G/C provides sustained high local antibiotics for at least 7 d with minimal systemic spillover, supporting further evaluation in orthopedic infection management.