The sustained release of antibiotic from freeze-dried fibrin-antibiotic compound and efficacies in a rat model of osteomyelitis.
The kinetics of drug release from fibrin adhesive agent (consisting of fibrinogen, factor 8, thrombin, aportinin and calcium chloride)-antibiotic compound and efficacy on rat experimental osteomyelitis were studied. To enhance the slow release activities of antibiotic, a mixture of fibrin clots was freeze-dried. Effects of freeze-drying were to make a fibrin clot an interlinked pore and to increase crosslinking rate containing an antibiotic. A diffusion test from aminoglycoside (Arbekacin Sulfate: 200 mg) compound was carried out. In vitro study freeze-dried antibiotic compound (FFAC: 1 cm3) was placed in saline (3 ml). The saline was replaced every 48 h and the previous solution was stored at -45 degrees C until assay. The result was that a concentration of 0.4 mg/l, sufficiently high to control Staphylococcus aureus strain IM2-42, was maintained within nine exchanges of saline after 18 days. In vivo animal experiments, FFAC (2 x 2 x 3 mm) were tested in rats with established Staphylococcus aureus osteomyelitis in the proximal tibia. The animals were observed for radiographic signs of infection and tissue was examined histopathologically. Bacterial counts by bone cultures were statistically lower in rats implanted with FFAC than in those only given a drug-free FFC and curettage. Radiographical and histological observations also showed beneficial effects of the FFAC. The results suggest that the FFAC provide a simple drug delivery system, and may be a promising alternative treatment for osteomyelitis.
Itokazu
M
M
Dept. of Orthopedic Surgery, Gifu University School of Medicine, Japan.
Yamamoto
K
K
Yang
W Y
WY
Aoki
T
T
Kato
N
N
Watanabe
K
K
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D002122:Calcium Chloride / Q000378:metabolism; D003982:Dibekacin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000378:metabolism / Q000494:pharmacology*; D005169:Factor VIII / Q000378:metabolism / Q000494:pharmacology; D015718:Fibrin Tissue Adhesive / Q000378:metabolism / Q000494:pharmacology*; D005340:Fibrinogen / Q000378:metabolism / Q000494:pharmacology; D005612:Freeze Drying; D008297:Male; D010019:Osteomyelitis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D015718:Fibrin Tissue Adhesive; D003982:Dibekacin; D005169:Factor VIII; D005340:Fibrinogen; D013917:Thrombin; C031986:arbekacin; D002122:Calcium Chloride