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Osteomyelitis Treatment with Nanometer-Sized Hydroxyapatite Particles as a Delivery Vehicle for a Ciprofloxacin- Bisphosphonate Conjugate; New Fluoroquinolone-Bisphosphonate Derivatives Show Similar Binding Affinity to Hydroxyapatite and Improved Antibacterial Activity Against Drug-Resistant Pathogens
DWIGHT DAVID EISENHOWER ARMY MEDICAL CENTER FORT GORDON GA DEPT OF CLINICAL INVESTIGATION
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Orthopaedic injuries comprise a majority of combat injuries seen in recent US military conflicts. The development and increased use of modern body armor, which has been correlated with decreased chest and upper abdominal injuries Mabry et al., 2000, will likely continue to result in an increased relative rate of extremity injuries. These injuries commonly present with significant open bone fractures of the limbs and substantial contamination with bacteria from high energy trauma. Once bone infection is established, one fourth of open fractures will progress to osteomyelitis OM Lew and Waldvogel, 1997 Wolski, 2004 Buxton et al., 2004. We developed a novel local drug-delivery system consisting of ciprofloxacin-bisphosphonate conjugate E41 bound to calcium phosphate CP bone particles. In situ, the conjugate dissociates from CP and maintains its antibacterial activity. This topical granulated antibiotic delivery system reduced infection rates in our in vivo OM model. Current studies contrast two CP homeostatic bone-substitute particles, nanometer-sized hydroxyapatite NanOssTrademark Nan, and mu-sized tricalcium phosphate SkeliteTrademark TCP in vitro for binding to E41, and in vivo for E41-CP blockade of rat OM.
APPROVED FOR PUBLIC RELEASE