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Prevention of Orthopedic Device-Associated Osteomyelitis Using Oxacillin-Containing Biomineral-Binding Liposomes

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ABSTRACT

Purpose

To develop novel biomineral-binding liposomes (BBL) for the prevention of orthopedic implant associated osteomyelitis.

Methods

A biomineral-binding lipid, alendronate-tri(ethyleneglycol)-cholesterol conjugate (ALN-TEG-Chol), was synthesized through Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (a versatile click reaction). Mixing with other excipients, the new lipid was used to develop BBL. Thermodynamic behavior was studied by differential scanning calorimetry (DSC). In vitro biomineral-binding potential and kinetics were evaluated on hydroxyapatite (HA, a widely used material for orthopedic implant devices) particles. Oxacillin was encapsulated into BBL and used for in vitro evaluation in preventing Staphylococcus aureus biofilm formation.

Results

DSC analysis showed that ALN-TEG-Chol could inhibit the phase transition of liposomes by reducing its cooperativity, yielding liposomes with thermodynamic stability similar to liposomes containing regular cholesterol. BBL showed fast and strong binding ability to HA. Oxacillin-loading BBL demonstrated significantly better preventive efficacy against bacteria colonization when challenged with S. aureus isolate, implying its potential in preventing orthopedic implant associated osteomyelitis.

Conclusions

In this proof of concept study, novel BBL has been successfully developed and validated for reducing the frequency of implantable device-related infections.

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported in part by NIH grants R01 AI038901 (KWB), P01 AI83211 (KWB), R01 AR053325 (DW), a NSF grant MCB-1122029 (LAM) and an Innovation Grant from UNeMed Corporation (DW).

Author information

Author notes

  1. Xin-Ming Liu

    Present address: Department of Pharmacology and Experimental Neurosciences Durham Research Center 3046, University of Nebraska Medical Center, 985800 Nebraska Medical Center, Omaha, Nebraska, 68198-5800, USA

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, COP 3026, Omaha, NE, 68198-6025, USA

    Xin-Ming Liu, Yijia Zhang, Fu Chen, Irine Khutsishvili, Luis A. Marky & Dong Wang

  2. Department of Orthopaedic Surgery and Rehabilitation, University of Nebraska Medical Center, 981080 Nebraska Medical Center, Omaha, Nebraska, 68198-1080, USA

    Edward V. Fehringer

  3. Department of Pathology and Microbiology, University of Nebraska Medical Center, 983135 Nebraska Medical Center, Omaha, Nebraska, 68198-3135, USA

    Kenneth W. Bayles

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  1. Xin-Ming Liu
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  2. Yijia Zhang
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  3. Fu Chen
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  8. Dong Wang
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Corresponding author

Correspondence to Dong Wang.

Additional information

Xin-Ming Liu and Yijia Zhang contributed equally to this work.

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Liu, XM., Zhang, Y., Chen, F. et al. Prevention of Orthopedic Device-Associated Osteomyelitis Using Oxacillin-Containing Biomineral-Binding Liposomes. Pharm Res 29, 3169–3179 (2012). https://doi.org/10.1007/s11095-012-0812-7

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  • DOI: https://doi.org/10.1007/s11095-012-0812-7

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