Antibacterial Effects of Controlled Antibiotic Release Using Antibiotic-LDH Hybrids

Lee, Han Yong; Lee, Yoon Min; Lee, Kyung Won

Abstract

PURPOSE: To evaluate an effect of controlled antibiotic release of the layered double hydroxides (LDH) as a new drug delivery system, and to observe a histological changes of the LDH in vivo and the differences of antibacterial effects among the several antibiotic-LDH hybrids.
MATERIALS AND METHODS
Staphylococcus aureus (ATCC 23235) and Escherchia coli (ATCC 10536) were used as a bacterial specimens. Antibiotic-LDH hybrids were gentamicin-LDH (GM-LDH), cefaclor-LDH (CCLO-LDH), cefuroxime axetil-LDH (CRXMA-LDH) and ceftazidime-LDH (CAZ-LDH). In vitro study, two methods were used. One was dilution method, used to determine the minimum inhibitory concentrations (MICs) of the antibiotic-LDH hybrids. The other one was disk diffusion method, to observe the zones of bacterial inhibition of them. In vivo forty New Zealand White rabbits (2.5~3.0 kg) were divided into 10 groups. Animals were anesthetized and a 3 mm-diameter hole was drilled 2 cm proximal to the distal end of the left femur. The antibiotic-LDH hybrids was put into the drilled hole and then 0.1 ml (105 CFU/ml) of S. aureus and E. coli were inoculated into the drilled hole in each group. Histological examination was done at postoperative 1, 2, 3, and 4 weeks respectively.
RESULTS
The MICs for S. aureus were more than 400 microgram/ml in GM-LDH, 25 microgram/ml in CRXMA-LDH, 25 microgram/ml in CCLO-LDH, and 100 microgram/ml in CAZ-LDH. The MICs for E. coli were 12.5 microgram/ml in GM-LDH, 25 microgram/ml in CRXMA-LDH, 25 microgram/ml in CCLO-LDH, and 1.56 microgram/ml in CAZ-LDH. CCLO-LDH was effective on both S. aureus and E. coli and CRXMA-LDH on E. coli in disk diffusion method. In contrast, GM-LDH and CAZ-LDH were not effective on neither S. aureus nor E. coli. Histologically, LDH was shown as large masses at the postoperative 1~2 weeks and changed to several small masses or fragments at the postoperative 3~4 weeks.
CONCLUSION
There was much difference of the extent of controlled antibiotic release among antibiotic-LDH hybrids. The size and volume of LDH in vivo was reduced gradually. CCLO-LDH, and CRXMA-LDH seemed to have an effect of the bacterial growth inhibition.