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

10 Scopus citations

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)1-11
Number of pages11
JournalInternational Journal of Hyperthermia
DOIs
Publication statusAccepted/In press - Feb 16 2016

    Fingerprint

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Physiology
  • Radiological and Ultrasound Technology
  • Physiology (medical)

Cite this