Targeted antibiotic delivery using low temperature-sensitive liposomes and magnetic resonance-guided high-intensity focused ultrasound hyperthermia

Rachel Wardlow, Chenchen Bing, Joshua VanOsdol, Danny Maples, Michelle Ladouceur-Wodzak, Michele Harbeson, Joris Nofiele, Robert Staruch, Akhilesh Ramachandran, Jerry Malayer, Rajiv Chopra, Ashish Ranjan

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)254-264
Number of pages11
JournalInternational Journal of Hyperthermia
Volume32
Issue number3
DOIs
StatePublished - Apr 2 2016

Keywords

  • Chronic wound
  • MR-HIFU
  • image guided therapy
  • low temperature-sensitive liposomes (LTSL)
  • triggered antibiotic release

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cancer Research

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  • Cite this

    Wardlow, R., Bing, C., VanOsdol, J., Maples, D., Ladouceur-Wodzak, M., Harbeson, M., Nofiele, J., Staruch, R., Ramachandran, A., Malayer, J., Chopra, R., & Ranjan, A. (2016). Targeted antibiotic delivery using low temperature-sensitive liposomes and magnetic resonance-guided high-intensity focused ultrasound hyperthermia. International Journal of Hyperthermia, 32(3), 254-264. https://doi.org/10.3109/02656736.2015.1134818