Prevention of orthopedic device-associated osteomyelitis using oxacillin-containing biomineral-binding liposomes.
OBJECTIVE
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.
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, COP 3026, Omaha, NE 68198-6025, USA.
Xin-Ming
XM
Liu
Yijia
Y
Zhang
Fu
F
Chen
Irine
I
Khutsishvili
Edward V
EV
Fehringer
Luis A
LA
Marky
Kenneth W
KW
Bayles
Dong
D
Wang
D018441:Biofilms / Q000187:drug effects; D002152:Calorimetry, Differential Scanning / Q000379:methods; D061565:Cycloaddition Reaction / Q000379:methods; D005079:Excipients / Q000008:administration & dosage; D007700:Kinetics; D008081:Liposomes / Q000008:administration & dosage*; D009984:Orthopedic Fixation Devices / Q000382:microbiology*; D009985:Orthopedics / Q000379:methods; D010019:Osteomyelitis / Q000209:etiology / Q000382:microbiology / Q000517:prevention & control*; D010068:Oxacillin / Q000008:administration & dosage*; D044367:Phase Transition / Q000187:drug effects; D019736:Prostheses and Implants / Q000382:microbiology*; D013203:Staphylococcal Infections / Q000209:etiology / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000187:drug effects / Q000502:physiology; D013816:Thermodynamics
D005079:Excipients; D008081:Liposomes; D010068:Oxacillin