The effectiveness of the controlled release of gentamicin from polyelectrolyte multilayers in the treatment of Staphylococcus aureus infection in a rabbit bone model

Abstract

While the infection rate of orthopedic implants is low, the required treatment, which can involve six weeks of antibiotic therapy and two additional surgical operations, is life threatening and expensive, and thus motivates the development of a one-stage re-implantation procedure. Polyelectrolyte multilayers incorporating gentamicin were fabricated using the layer-by-layer deposition process for use as a device coating to deal with an existing bone infection in a direct implant exchange operation. The films eluted about 70% of their payload in vitro during the first three days and subsequently continued to release drug for more than four additional weeks, reaching a total average release of over 550 μg/cm 2 . The coatings were demonstrated to be bactericidal against Staphylococcus aureus, and degradation products were generally nontoxic towards MC3T3-E1 murine preosteoblasts. Film-coated titanium implants were compared to uncoated implants in an in vivo S. aureus bone infection model. After a direct exchange procedure, the antimicrobial-coated devices yielded bone homogenates with a significantly lower degree of infection than uncoated devices at both day four (p < 0.004) and day seven (p < 0.03). This study has demonstrated that a self-assembled ultrathin film coating is capable of effectively treating an experimental bone infection in vivo and lays the foundation for development of a multi-therapeutic film for optimized, synergistic treatment of pain, infection, and osteomyelitis.

Small-molecule-hosting nanocomposite films with multiple bacteria-triggered responses

“…20 The assembly of surface coatings via LbL deposition enables the inclusion of a broad range of components within conformal coatings and has been explored to construct contact-killing 21 or release-killing films. 22 Owing to the complexity of bacterial and biofilm metabolism and the limitations of each individual antibacterial defense path, reliable antibacterial protection of surfaces remains elusive. Therefore, new multifunctional coatings are being explored that combine releasekilling and contact-killing capabilities.…”

Sustained protein release from hydrogel microparticles using layer-by-layer (LbL) technology

“…Several studies were published on this family of polymers by P. Hammond's group but primarily in the form of LbL films coating solid surfaces (Wood et al, 2005;Macdonald et al, 2008;Moskowitz et al, 2010, Shukla et al, 2010. Hereby, we aim to take this one step further and investigate the potential of these biodegradable polymers in coating hydrogel microspheres.…”

Multimonth controlled small molecule release from biodegradable thin films

“…A common challenge in any small molecule drug delivery system is the incorporation and subsequent controlled release of poorly charged or low molecular weight species. Our laboratory has investigated a number of LbLbased biodegradable strategies for controlled small molecule release, including direct incorporation of drug into the film (21,22) and physical entrapment in other charged systems (23,24), with a longest sustained release of 3 wk. Changes in the aqueous environment, such as pH or ionic strength, also can facilitate undesirable film deterioration or drug elution that dramatically affects release kinetics (25).…”