Premium
Two fluoroquinolone‐bisphosphonate (BP) derivatives show similar binding affinity to calcium phosphate (CP) particles, but have different antibacterial activity
Author(s) -
Buxton Thomas Brooks,
Runner Royce R,
Herczegh Pal,
McPherson James C
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1136.23
Subject(s) - chemistry , dissociation constant , staphylococcus aureus , ciprofloxacin , calcium , microbiology and biotechnology , minimum inhibitory concentration , pharmacology , in vitro , antibiotics , biochemistry , bacteria , medicine , receptor , biology , organic chemistry , genetics
We previously demonstrated that osteoadsorptive BP conjugates of fluoroquinolones (E41, ciprofloxacin‐BP), carried on CP particles (μ‐sized Skelite™), packed into a traumatized bony defect, showed value in the treatment of rat tibial osteomyelitis (British J Surg, 2004;91:1192–1196). A Gatifloxacin‐BP conjugate (GB) was contrasted to E41 for activity against methicillin‐susceptible Staphylococcus aureus , and other pathogens. Minimum inhibitory concentration (MIC) and Mininum Bactericidal Concentrations (MBC) were determined. In vitro binding studies, holding levels of E41 and GB constant (2 μg/ml), while increasing levels of CP (nm‐sized NanOss™), were determined by measurement of fluoroquinolone‐BP associated fluorescence. GB showed greater MIC and MBC activity against several Gram‐positive and Gram‐negative pathogens, e.g., an 8‐fold difference with S. aureus (Table). Binding appeared to be saturable. Maximal binding was: E41, 89.7 % ± 4.74, vs. GB, 76.8 % ± 2.35 (p≤0.05). The dissociation constant was: E41, 1.35 × 10 −8 mM (NanOss™), vs GB, 1.83 × 10 −8 mM (p≤0.05). Versus E41, GB has ( i ) improved activity against bone‐pathogenic S. aureus, and other bacteria, and ( ii ) shows a similar binding affinity to NanOss™, used as a CP vehicle for topical drug delivery.