Sustained release of ciprofloxacin from an osteoconductive poly(DL)-lactide implant

Abstract

BACKGROUND AND PURPOSE: Antibiotic-releasing bioresorbable implants are used for local treatment of bone infections, but most drug delivery systems release antibiotic for too short a time. METHODS: We used pellets (0.9 x 1.0 mm) made of bioabsorbable poly(DL) lactic acid matrix, ciprofloxacin (7.3 +/- 0.4 wt%), and bioactive glass microspheres of 90-125 microm (29.3 +/- 0.2 wt%). The ciprofloxacin release and antibacterial activity was measured in elution tests in vitro and local tissue concentrations were measured in rabbits. RESULTS: In elution tests in vitro, the therapeutic level (> 2 microg/mL) of ciprofloxacin was achieved within 6 h of the start of the test, and it was maintained for up to 300 days. The antibacterial activity of the antibiotic released from sterilized composites was similar to that of the unprocessed ciprofloxacin. In vivo measurements showed high local tissue concentrations (16-86 micrg/g of bone tissue) for 3 months. Compared to previous experiments on two-component polymeric matrices (PLGA or PDLLA) with ciprofloxacin alone, adding bioactive glass microspheres into the composite resulted in morphological changes that facilitated fluid intrusion into the microstructure and quickened ciprofloxacin release. INTERPRETATION: This type of composition of implant may fulfill the requirements of bone infection therapy, for sustained local release of the selected antibiotic over several months.