Polymeric nanofiber coating with tunable combinatorial antibiotic delivery prevents biofilm-associated infection in vivo

Ashbaugh, Alyssa G.; Jiang, Xuesong; Zheng, Jesse; Tsai, Andrew; Kim, Woo Shin; Thompson, J. M. T.; Miller, Robert J.; Shahbazian, Jonathan H.; Wang, Yu; Dillen, Carly; Ordoñez, Alvaro A.; Chang, Yong S.; Jain, Sanjay; Jones, Lynne C.; Sterling, Robert S.; Mao, Hai‐Quan; Miller, Lloyd S.

doi:10.1073/pnas.1613722113

Cited by 89 publications

(76 citation statements)

References 53 publications

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“…Recent in vivo studies demonstrated the feasibility and efficacy of tunable multi-layer nanocoatings that released different combinations of antibiotics 129 or sequential delivery of gentamicin and an osteoinductive growth factor 130 in a time-staggered manner for prevention of biofilm-associated infection and bone tissue repair around implants. Both studies demonstrated the ability to prevent biofilm formation on the device surface, relative to uncoated controls, with the nanocoatings able to clear infiltrating bacteria and prevented colonization of the implant while promoting bone formation and osseointegration.…”

Section: The Promise Of New Technologiesmentioning

confidence: 99%

Targeting microbial biofilms: current and prospective therapeutic strategies

et al. 2017

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Biofilm formation is a key virulence factor for a wide range of microorganisms that cause chronic infections. The multifactorial nature of biofilm development and drug tolerance imposes great challenges for the use of conventional antimicrobials, and indicates the need for multi-targeted or combinatorial therapies. In this review, we focus on current therapeutic strategies and those that are under development that target vital structural and functional traits of microbial biofilms and drug tolerance mechanisms, including the extracellular matrix and dormant cells. We emphasize strategies that are supported by in vivo or ex vivo studies, highlight emerging biofilm-targeting technologies, and provide a rationale for multi-targeted therapies that are aimed at disrupting the complex biofilm microenvironment.

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Section: The Promise Of New Technologiesmentioning

confidence: 99%

Targeting microbial biofilms: current and prospective therapeutic strategies

et al. 2017

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“…We found that the coatings with combinatorial release of vancomycin, daptomycin, or linezolid in conjunction with rifampin prevented a S. aureus (Xen36) infection in our K‐wire mouse model of OIAI . Moreover, using a near‐infrared fluorescent dye as a surrogate for antibiotic release from the coating, in vivo FLI imaging was employed to quantify and determine the duration of release of the fluorescent dye from the coating . Of note, the coating with combinatorial linezolid and rifampin release also prevented an MRSA (SAP231) infection in our rabbit model of OIAI .…”

Section: Treatmentmentioning

confidence: 80%

“…We found that the minocycline and rifampin‐releasing implant coating prevented the development of a S. aureus (strain ALC2906) infection in our K‐wire mouse model of OIAI . In addition, we used in vivo BLI imaging to evaluate the efficacy of a novel implant coating composed of poly(lactic‐co‐glycolic acid) and poly(ε‐caprolactone) nanofibers impregnated with single or combinatorial antibiotics . We found that the coatings with combinatorial release of vancomycin, daptomycin, or linezolid in conjunction with rifampin prevented a S. aureus (Xen36) infection in our K‐wire mouse model of OIAI .…”

Section: Treatmentmentioning

confidence: 95%

“…In addition, we used in vivo BLI imaging to evaluate the efficacy of a novel implant coating composed of poly(lactic‐co‐glycolic acid) and poly(ε‐caprolactone) nanofibers impregnated with single or combinatorial antibiotics . We found that the coatings with combinatorial release of vancomycin, daptomycin, or linezolid in conjunction with rifampin prevented a S. aureus (Xen36) infection in our K‐wire mouse model of OIAI . Moreover, using a near‐infrared fluorescent dye as a surrogate for antibiotic release from the coating, in vivo FLI imaging was employed to quantify and determine the duration of release of the fluorescent dye from the coating .…”

Section: Treatmentmentioning

confidence: 99%

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Preclinical Optical Imaging to Study Pathogenesis, Novel Therapeutics and Diagnostics Against Orthopaedic Infection

Thompson

Miller

2019

Journal Orthopaedic Research

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Preclinical in vivo optical imaging includes bioluminescence imaging (BLI) and fluorescence imaging (FLI), which provide noninvasive and longitudinal monitoring of biological processes in an in vivo context. In vivo BLI involves the detection of photons of light from bioluminescent bacteria engineered to naturally emit light in preclinical animal models of infection. Meanwhile, in vivo FLI involves the detection of photons of a longer emission wavelength of light after exposure of a fluorophore to a shorter excitation wavelength of light. In vivo FLI has been used in preclinical animal models to detect fluorescent‐labeled host proteins or cells (often in engineered fluorescent reporter mice) to understand host‐related processes, or to detect injectable near‐infrared fluorescent probes as a novel approach for diagnosing infection. This review describes the use of in vivo optical imaging in preclinical models of orthopaedic implant‐associated infection (OIAI), including (i) pathogenesis of the infectious course, (ii) monitoring efficacy of antimicrobial prophylaxis and therapy and (iii) evaluating novel near‐infrared fluorescent probes for diagnosing infection. Finally, we describe optoacoustic imaging and fluorescence image‐guided surgery, which are recent technologies that have the potential to translate to diagnosing and treating OIAI in humans. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2269–2277, 2019

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“…63 Polymeric nanofibers, composed of PLGA and PCL, were developed by Ashbaugher et al for local co-delivery of a combination of antibiotics. 80 The release can be adjusted by varying the PLGA/PCL polymer ratio and proved to be highly effective in preventing medical device infections in patients. Benoit and co-workers synthesized positively charged nanoparticles from diblock copolymers composed of 2-(dimethylamino)ethyl methacrylate (DMAEMA), butyl methacrylate (BMA) and 2-propylacrylic acid (PAA) for loading with farnesil, a hydrophobic antibacterial drug.…”

Section: Polymer Nanoparticles and Hydrogelsmentioning

confidence: 99%

Advancements on the molecular design of nanoantibiotics: current level of development and future challenges

Jijie

Barras

Teodorescu

et al. 2017

Mol. Syst. Des. Eng.

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Abstract.Numerous antimicrobial drugs have been developed and commercialized to kill and inhibit the growth of pathogenic microbes. The therapeutic efficiency of these drugs has however become often inadequate for the treatment of microbial infections, the reasons being multiple. Oral administration results often in only partial absorption and up to 50% of the active compound can be excreted in the urine. Furthermore, antibiotic therapy is also frequently accompanied by gastrointestinal complications, including vomiting, nausea and diarrhea. From a therapeutic point of view, the low solubility of antibiotics in lipid membranes presents a limitation for rapid and efficient treatment of infections. The preferred route for the delivery of antimicrobial drugs is the oral one; oral formulations capable of extending the duration of drug delivery and minimizing side effects have received much attention. The combination of antimicrobial agents with nanomaterials has been seen as a particularly promising strategy to overcome these limitations. Particulate formulations have proven their efficiency in achieving better pharmacokinetic profiles and improving the bio availability of several antibiotics. Antibiotic modified particles have shown their capability to protect some of the antimicrobial drugs from stomach acid and first-pass metabolisms in the gastrointestinal tract. Likewise, particle formulations can increase the circulation times of a drug and the local concentration gradient across absorptive cells. The present review describes the current status of different types of antibiotic loaded nano-systems. Key principles such as antibiotic loading, the release mechanism and the mode of action involved in pathogen killing or inhibition will be discussed in more detail. It is hoped that the general knowledge obtained here will help in the generation of advanced nanomaterials loaded with antimicrobials agents.Post-print 2

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Polymeric nanofiber coating with tunable combinatorial antibiotic delivery prevents biofilm-associated infection in vivo

Cited by 89 publications

References 53 publications

Targeting microbial biofilms: current and prospective therapeutic strategies

Targeting microbial biofilms: current and prospective therapeutic strategies

Preclinical Optical Imaging to Study Pathogenesis, Novel Therapeutics and Diagnostics Against Orthopaedic Infection

Advancements on the molecular design of nanoantibiotics: current level of development and future challenges

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