Abstract
INTRODUCTION
We have conducted interface bioactive bone cement method (IBBC) in total hip arthoplasty (THA) to prevent generation of connective tissue and osteolysis for the longevity of cemented THA since 1985, in which non-resorbable crystalline osteoconductive hydroxyapatite (HA) granules were interposed on the interface between bone and bone cement. To prevent the patients from infection, we use HA granules impregnated with antibiotics. However, there have been no reports on the loading and release of antibiotics from fine granules of HA. Here, we have investigated the loading of antibiotics on HA and their release in vitro.
MATERIALS AND METHODS
HA 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, HA 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 antibiotic solution to HA granules, the amount of antibiotic released from 20 mg of HA was 16 μg for F, 0 μg for V, 13 μg for C and 65 μg for CE. The release of F continued for 48 hrs and that of V and CEcompleted within 24 hrs. On the other hand, when antibiotics loading were conducted under reduced pressure, the amount of released antibiotic was 14 μg for F, 0 μg for V, 0 μg for C and 1670 μg for CE. The burst release was observed for CE and F, and the release of them completed in 24 hrs. Then, the release of C and CE was observed in 0.025 M EDTA solution after the antibiotic was loaded under pressure. Observation was done for 19 days, at which one third of HA was dissolved. After 40 μg of burst release, the release of C continued for 19 days, at which the total amount of C released was 122 μg. Meanwhile, the release of CE continued over 19 days, during which 3350μg of CE was released after the burst release of 3280 μg. Thus, CE seemed the most suitable antibiotic for our purpose. The burst release of CE absorbed in HA following the issue of CE surrounding the HA granules on the interface of bone and bone cement is very effective for the protection of early infection after joint replacement.
