Treating methicillin-resistant Staphylococcus aureus (MRSA) bone infection with focused ultrasound combined thermally sensitive liposomes.
Int J Hyperthermia
; 40(1): 2211278, 2023.
Article
en En
| MEDLINE
| ID: mdl-37437891
ABSTRACT
OBJECTIVE:
Chronic bone infection caused by Staphylococcus aureus biofilms in children and adults is characterized by reduced antibiotic sensitivity. In this study, we assessed 'heat-targeted, on-demand' antibiotic delivery for S. aureus killing by combining ciprofloxacin (CIP)-laden low-temperature sensitive liposomes (LTSLs) with local high-intensity focused ultrasound (HIFU) induced bone heating in a rat model of bone infection.METHODS:
CIP-LTSLs were prepared using the thin-film hydration and extrusion method. Bone infection was established by surgically implanting an orthopedic K-wire colonized with methicillin-resistant S. aureus (MRSA) strain into rat's femurs. For bone heating, ultrasound-guided HIFU exposures were performed to achieve a local temperature of 40-42 °C (â¼15 min) concurrently with intravenous injection of CIP-LTSLs or CIP. CIP biodistribution was determined spectrophotometrically and therapeutic efficacy was determined by bacteriological, histological and scanning electron microscopy (SEM) analyses.RESULTS:
CIP-LTSLs in the range of 183.5 nm ± 1.91 showed an encapsulation efficiency of >70% at 37 °C and a complete release at â¼42 °C. The metal implantation method yielded medullary osteomyelitis characterized by suppurative changes (bacterial and pus pockets) by day 10 in bones and adjoining muscle tissues. HIFU heating significantly improved CIP delivery from LTSLs in bones, resulting in a significant reduction in MRSA load compared to HIFU and CIP alone groups. These were also verified by histology and SEM, wherein a distinct reduction in S. aureus population in the infected metal wires and tissues from the combinatorial therapy was noted.CONCLUSION:
HIFU improved CIP delivery to bones, achieving clearance of hard-to-treat MRSA biofilms.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Osteomielitis
/
Staphylococcus aureus Resistente a Meticilina
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Año:
2023
Tipo del documento:
Article