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.

Original languageEnglish (US)
Pages (from-to)3169-3179
Number of pages11
JournalPharmaceutical Research
Volume29
Issue number11
DOIs
StatePublished - Nov 1 2012

Fingerprint

Oxacillin
Orthopedics
Osteomyelitis
Liposomes
Equipment and Supplies
Alendronate
Cholesterol
Differential Scanning Calorimetry
Thermodynamics
Staphylococcus aureus
Differential scanning calorimetry
Lipids
Cycloaddition
Excipients
Phase Transition
Cycloaddition Reaction
Biofilms
Durapatite
Bacteria
Thermodynamic stability

Keywords

  • bisphosphonates
  • liposomes
  • orthopaedic implant
  • osteomyelitis
  • oxacillin

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Prevention of orthopedic device-associated osteomyelitis using oxacillin-containing biomineral-binding liposomes. / Liu, Xin Ming; Zhang, Yijia; Chen, Fu; Khutsishvili, Irine; Fehringer, Edward V.; Marky, Luis A; Bayles, Kenneth W; Wang, Dong.

In: Pharmaceutical Research, Vol. 29, No. 11, 01.11.2012, p. 3169-3179.

Research output: Contribution to journalArticle

Liu, Xin Ming ; Zhang, Yijia ; Chen, Fu ; Khutsishvili, Irine ; Fehringer, Edward V. ; Marky, Luis A ; Bayles, Kenneth W ; Wang, Dong. / Prevention of orthopedic device-associated osteomyelitis using oxacillin-containing biomineral-binding liposomes. In: Pharmaceutical Research. 2012 ; Vol. 29, No. 11. pp. 3169-3179.
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