Abstract
INTRODICTION
Since 1985, not resorbable crystalline osteoconductive hydroxyapatite (HA) granules were interposed on the interface between bone and bone cement at the cementation (Interface Bioactive Bone Cement: IBBC) of total hip arthoplasty (THA) to prevent generation of connective tissue and osteolysis for the longevity of cemented THA. To prevent the patients from infection, we are planning to use b-tricalcium phosphate (Beta-TCP) impregnated with antibiotics along with HA granules. However, there have been no reports on the loading and release of antibiotics from fine granules of Beta-TCP. Here, we have investigated the loading of antibiotics on Beta-TCP and their release in vivo.
MATERIALS AND METHODS
Beta-TCP was impregnated with antibiotics such as flomoxef sodium (F), vancomycin hydrochloride (V) cefotiam dihydrochloride (C) and cefozopran hydrochloride (CE) under normal or reduced pressure. After washing with PBS three times, Beta-TCP loaded with the antibiotic was placed in PBS. An aliquot of solution was sampled at appropriate time intervals and the amount of the released antibiotic was estimated based on the anti-bacterial activity.
RESULTS AND DISCUSSION
When drug loading was done by dropping the antibiotic solution to Beta-TCP granules, the amount of antibiotic released from 20 mg of HA was 8 μg forF, 0 μg for V, 6 μg for C and 520 μg for CE. Their release completed within 24 hrs. When the antibiotic loading was done under reduced pressure, 20 mg of Beta-TCP was loaded with 40 μg ofF, 130 μg of V and 25 μg of C, but the released amount was 16 μg for F, 8 μg for V and 0 μg forC. Each drug was released within 10 hrs. Meanwhile, 8000 μg of CE was loaded on 20 mg of Beta-TCP and its release continued for 6 days. When Beta-TCP loaded with C or CE was placed in 0.25 MEDTA to dissolve Beta-TCP gradually, the release of C and CE sustained over 14 days along with the dissolution of Beta-TCP. The release of C from Beta-TCP continued over 19 days in EDTA. The released amount of C and CE were 116 μg and 7100 μg, respectively. Thus, CE seemed the most suitable for our purpose in terms of the loaded amount and releasing behavior. However, CE as well as C showed the eminent sustained release in EDTA solution. Since Beta-TCP shows bioabsoption, it is expected to be efficient antibiotics carrier. It is worthy to use adequate sizes of Beta-TCP granules impregnated with antibiotics in combination with osteoconductive HA in IBBC for the protection of the infection after joint replacement, especially in revision surgery after infection.
