Using Antibiotic Conjugated Magnetic Nanoparticles and a Magnetic Field for the Treatment of Bone Prosthetic Infections
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Using Antibiotic Conjugated Magnetic Nanoparticles and a Magnetic Field for the Treatment of Bone Prosthetic Infections Erik N. Taylor, George E. Aninwene II, and Thomas J. Webster School of Engineering and Department of Orthopedics, Brown University Providence, RI 02906, U.S.A. Abstract Bacterial infection of bone (called osteomyelitis) is of great concern to the medical community. In addition to bone, numerous medical devices are susceptible to microbial colonization when implanted. These infections are chronic since bacteria form a robust adhesion to surfaces, can be protected by sticky slime matrix (called a biofilm) from the body’s immune system (which would otherwise naturally clear the bacteria), and antibiotic treatments may not resolve such infections (due to antibiotic resistance). Here, the multifunctional properties of magnetic nanoparticles (termed here superparamagnetic iron oxide nanoparticles, or SPION) will be explored for their antibacterial activity, magnetic properties, and drug deliverable properties. This study provides a first step towards the development of a new type of pharmaceutical useful for orthopedic or other device related infections by demonstrating physical (magnetic) control of antibiotics towards bacteria and biofilms. Introduction Infection of bone and medical devices, such as those caused by Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis), are frequently chronic and painful to patients. Implant failure from infection is often mediated by matrix-enclosed surface associated bacteria (called biofilms), which are resistant to antibiotic treatment. Therefore, most believe that an infected prosthetic device must be physically removed before the infection can be resolved [1]. Recent studies estimate the infection burden on all revision surgeries is about 15% of for TKA and THA [2, 3]. Most bacteria found in prosthetic infections are Gram-positive and, furthermore, are commonly composed of S. aureus and S. epidermidis [4-6]. S. aureus biofilms have been found in about one-fourth of all prosthetic infections [4-6] and one-half of all reported cases of osteomyelitis [7]. In particular, methicillin resistant S. aureus (MRSA) has caused great concern for the spread of antibiotic resistant bacteria. A recent report estimates that the number of MRSA infections in hospitals has doubled nationwide, from approximately 127,000 in 1999 to 278,000 in 2005 [8]. S. epidermidis on the other hand is found ubiquitously on the human skin (for example, the patient’s skin, a likely source of contamination) as part of the normal bacterial flora [9]. S. epidermidis species are cited as being the most frequent isolated organism in prosthetic infection, found in about one-third (32-36%) of all infections [4, 5]. It might be possible to kill antibiotic resistant bacteria by simply increasing the concentration of the antibiotic, or by using an alternative approach all together. SPION, or other biocompatible magnetic nanoparticles, have been previously used for magnetic
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