Two-month ciprofloxacin implants for multibacterial bone infections.

Area of Science:

• Biomaterials Science
• Orthopedic Surgery
• Infectious Diseases

Background:

• Multibacterial bone infections, such as osteomyelitis, pose significant treatment challenges.
• Effective local antibiotic delivery is crucial for eradicating pathogens and promoting bone healing.
• Existing treatments often struggle with achieving sustained therapeutic drug concentrations at the infection site.

Purpose of the Study:

• To characterize an in vivo ciprofloxacin implant formulation for treating multibacterial bone infections.
• To evaluate the release kinetics and therapeutic efficacy of the implant in a rabbit model.
• To assess the biocompatibility and osteoconductive properties of the implant materials.

Main Methods:

• A ciprofloxacin implant (40% ciprofloxacin, 12% hydroxyapatite, 36% tricalcium phosphate, 12% poly(DL-lactide)) was surgically inserted into rabbit femurs.
• Ciprofloxacin release levels were quantified over 8 weeks using validated assays.
• Femur and tibia tissues were analyzed for antibiotic concentrations relative to minimum inhibitory concentrations (MIC).
• Implant degradation, morphological, and crystallographic changes were assessed using X-ray analysis.

Main Results:

• Approximately 90% of ciprofloxacin was released within 8 weeks, maintaining femur and tibia therapeutic levels.
• Antibiotic concentrations exceeded MIC for common osteomyelitis pathogens in femoral cortex and marrow throughout the study.
• Tibia cortex levels remained above MIC for 6 weeks post-implantation.
• X-ray analysis confirmed the implant's osteoconductivity and biocompatibility, showing normal bone repair responses.

Conclusions:

• The ciprofloxacin implant formulation effectively delivers sustained therapeutic antibiotic levels for bone infections.
• Implant erosion and bone ingrowth into the hydroxyapatite/tricalcium phosphate/poly(DL-lactide) matrix enhance ciprofloxacin release, influenced by its low solubility.
• The formulation demonstrates excellent biocompatibility and osteoconductivity, supporting its potential for clinical use in treating osteomyelitis.