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


CONCLUSIONS
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.
Koort
Jyri K
JK
Department of Orthopaedic Surgery and Traumatology, University of Turku, Orthopaedic Research Unit, Turku, Finland.
Makinen
Tatu J
TJ
Suokas
Esa
E
Veiranto
Minna
M
Jalava
Jari
J
Tormala
Pertti
P
Aro
Hannu T
HT
D020341:Absorbable Implants; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004343:Drug Implants; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008863:Microspheres; D010019:Osteomyelitis / Q000188:drug therapy* / Q000382:microbiology; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011108:Polymers; D011817:Rabbits
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D003692:Delayed-Action Preparations; D004343:Drug Implants; D011108:Polymers; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002939:Ciprofloxacin