CarboCell G/C offers high and prolonged concentrations of gentamicin and clindamycin in bone tissue following intraosseous injection

<b>Objectives</b>: The novel local antibiotic-eluting depot technology CarboCell G/C has shown great promise in terms of efficacy in an osteomyelitis pig model. The present study aimed to investigate the initial release kinetics of gentamicin and clindamycin from CarboCell G/C in trabecular bone after a thin-needle intraosseous injection. <b>Methods</b>: In the tibial metaphysis of four pigs (both hind legs, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>n</mml:mi> <mml:mo>=</mml:mo> <mml:mn>8</mml:mn></mml:mrow> </mml:math> ), microdialysis catheters were placed 5 and 10 mm from an intraosseous injected CarboCell G/C depot of 1.5 mL comprising gentamicin (25 mg) and clindamycin (95 mg). Sampling was performed for 12 consecutive hours to evaluate gentamicin and clindamycin concentrations in trabecular bone and subcutaneous tissue adjacent to the knee joint. Plasma samples were taken to determine systemic spillover. <b>Results</b>: Across trabecular bone locations, the mean peak drug concentrations ranged from 471-524 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>µ</mml:mi></mml:mrow> </mml:math> g mL^-1 for gentamicin and from 681-788 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>µ</mml:mi></mml:mrow> </mml:math> g mL^-1 for clindamycin. The mean concentrations at 12 h ranged from 126-321 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>µ</mml:mi></mml:mrow> </mml:math> g mL^-1 for gentamicin and from 255-594 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>µ</mml:mi></mml:mrow> </mml:math> g mL^-1 for clindamycin. Low concentrations of both drugs were found in subcutaneous tissue adjacent to the knee joint ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mo><</mml:mo> <mml:mn>1</mml:mn></mml:mrow> </mml:math> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>µ</mml:mi></mml:mrow> </mml:math> g mL^-1) and plasma ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mo><</mml:mo> <mml:mn>0.2</mml:mn></mml:mrow> </mml:math> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>µ</mml:mi></mml:mrow> </mml:math> g mL^-1). <b>Conclusions</b>: CarboCell G/C can maintain high local concentrations of gentamicin and clindamycin for at least 12 h after intraosseous injection with negligible systemic spillover. The data bolster the potential benefit of improved local antibiotic delivery systems with flexible administration in target tissues for future therapeutic strategies addressing orthopaedic infections.