TY - JOUR
T1 - Targeted antibiotic delivery using low temperature-sensitive liposomes and magnetic resonance-guided high-intensity focused ultrasound hyperthermia
AU - Wardlow, Rachel
AU - Bing, Chenchen
AU - VanOsdol, Joshua
AU - Maples, Danny
AU - Ladouceur-Wodzak, Michelle
AU - Harbeson, Michele
AU - Nofiele, Joris
AU - Staruch, Robert
AU - Ramachandran, Akhilesh
AU - Malayer, Jerry
AU - Chopra, Rajiv
AU - Ranjan, Ashish
N1 - Publisher Copyright:
© 2016 Taylor & Francis.
PY - 2016/4/2
Y1 - 2016/4/2
N2 - Abstract: Chronic non-healing wound infections require long duration antibiotic therapy, and are associated with significant morbidity and health-care costs. Novel approaches for efficient, readily-translatable targeted and localised antimicrobial delivery are needed. The objectives of this study were to 1) develop low temperature-sensitive liposomes (LTSLs) containing an antimicrobial agent (ciprofloxacin) for induced release at mild hyperthermia (∼42 °C), 2) characterise in vitro ciprofloxacin release, and efficacy against Staphylococcus aureus plankton and biofilms, and 3) determine the feasibility of localised ciprofloxacin delivery in combination with MR-HIFU hyperthermia in a rat model. LTSLs were loaded actively with ciprofloxacin and their efficacy was determined using a disc diffusion method, MBEC biofilm device, and scanning electron microscopy (SEM). Ciprofloxacin release from LTSLs was assessed in a physiological buffer by fluorescence spectroscopy, and in vivo in a rat model using MR-HIFU. Results indicated that < 5% ciprofloxacin was released from the LTSL at body temperature (37 °C), while >95% was released at 42 °C. Precise hyperthermia exposures in the thigh of rats using MR-HIFU during intravenous (i.v.) administration of the LTSLs resulted in a four fold greater local concentration of ciprofloxacin compared to controls (free ciprofloxacin + MR-HIFU or LTSL alone). The biodistribution of ciprofloxacin in unheated tissues was fairly similar between treatment groups. Triggered release at 42 °C from LTSL achieved significantly greater S. aureus killing and induced membrane deformation and changes in biofilm matrix compared to free ciprofloxacin or LTSL at 37 °C. This technique has potential as a method to deliver high concentration antimicrobials to chronic wounds.
AB - Abstract: Chronic non-healing wound infections require long duration antibiotic therapy, and are associated with significant morbidity and health-care costs. Novel approaches for efficient, readily-translatable targeted and localised antimicrobial delivery are needed. The objectives of this study were to 1) develop low temperature-sensitive liposomes (LTSLs) containing an antimicrobial agent (ciprofloxacin) for induced release at mild hyperthermia (∼42 °C), 2) characterise in vitro ciprofloxacin release, and efficacy against Staphylococcus aureus plankton and biofilms, and 3) determine the feasibility of localised ciprofloxacin delivery in combination with MR-HIFU hyperthermia in a rat model. LTSLs were loaded actively with ciprofloxacin and their efficacy was determined using a disc diffusion method, MBEC biofilm device, and scanning electron microscopy (SEM). Ciprofloxacin release from LTSLs was assessed in a physiological buffer by fluorescence spectroscopy, and in vivo in a rat model using MR-HIFU. Results indicated that < 5% ciprofloxacin was released from the LTSL at body temperature (37 °C), while >95% was released at 42 °C. Precise hyperthermia exposures in the thigh of rats using MR-HIFU during intravenous (i.v.) administration of the LTSLs resulted in a four fold greater local concentration of ciprofloxacin compared to controls (free ciprofloxacin + MR-HIFU or LTSL alone). The biodistribution of ciprofloxacin in unheated tissues was fairly similar between treatment groups. Triggered release at 42 °C from LTSL achieved significantly greater S. aureus killing and induced membrane deformation and changes in biofilm matrix compared to free ciprofloxacin or LTSL at 37 °C. This technique has potential as a method to deliver high concentration antimicrobials to chronic wounds.
KW - Chronic wound
KW - MR-HIFU
KW - image guided therapy
KW - low temperature-sensitive liposomes (LTSL)
KW - triggered antibiotic release
UR - http://www.scopus.com/inward/record.url?scp=84958762079&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84958762079&partnerID=8YFLogxK
U2 - 10.3109/02656736.2015.1134818
DO - 10.3109/02656736.2015.1134818
M3 - Article
C2 - 26892114
AN - SCOPUS:84958762079
SN - 0265-6736
VL - 32
SP - 254
EP - 264
JO - International Journal of Hyperthermia
JF - International Journal of Hyperthermia
IS - 3
ER -