Temperature-sensitive liposomal ciprofloxacin for the treatment of biofilm on infected metal implants using alternating magnetic fields

Abstract

Implants are commonly used as a replacement for damaged tissue. Many implants, such as pacemakers, chronic electrode implants, bone screws, and prosthetic joints, are made of or contain metal. Infections are one of the difficult to treat complications associated with metal implants due to the formation of biofilm, a thick aggregate of extracellular polymeric substances (EPS) produced by the bacteria. In this study, we treated a metal prosthesis infection model using a combination of ciprofloxacin-loaded temperature-sensitive liposomes (TSL) and alternating magnetic fields (AMF). AMF heating is used to disrupt the biofilm and release the ciprofloxacin-loaded TSL. The three main objectives of this study were to (1) investigate low- and high- temperature-sensitive liposomes (LTSLs and HTSLs) containing the antimicrobial agent ciprofloxacin for temperature-mediated antibiotic release, (2) characterize in vitro ciprofloxacin release and stability, and (3) study the efficacy of combining liposomal ciprofloxacin with AMF against Pseudomonas aeruginosa biofilms grown on metal washers. The release of ciprofloxacin from LTSL and HTSL was assessed in physiological buffers. Results demonstrated a lower transition temperature for both LTSL and HTSL formulations when incubated in serum as compared with PBS, with a more pronounced impact on the HTSLs. Upon combining AMF with temperature-sensitive liposomal ciprofloxacin, a 3 log reduction in CFU of Pseudomonas aeruginosa in biofilm was observed. Our initial studies suggest that AMF exposure on metal implants can trigger release of antibiotic from temperature sensitive liposomes for a potent bactericidal effect on biofilm.

Alternating magnetic fields and antibiotics eradicate biofilm on metal in a synergistic fashion

“…SEM was conducted as follows. Biofilms cultured from P. aeruginosa (MB699) were prepared on rings and exposed to iAMF ( T max = 65 °C, Δ t exp = 5 min, dosing duration 1 h) and incubated in 10 mL MHII media with 64 μg mL −1 ciprofloxacin or 64 μg mL −1 meropenem for 12 h. Then the rings with biofilm were prepared for SEM, following a similar protocol described previously 40 . The rings were carefully transferred to 4 mL PBS, rinsed in 4 mL of 0.1 M sodium cacodylate buffer three times, and fixed for 24 h in 4 mL of 2% glutaraldehyde, 2% paraformaldehyde in 0.1 M sodium cacodylate buffer.…”

Biological and Physiochemical Methods of Biofilm Adhesion Resistance Control of Medical-Context Surface

“…The feasibility and safety of using alternating magnetic fields (AMF) exposures to eradicate biofilm on metal surfaces has been proved, and magnetic iron oxide and similar nanoparticles has been increasingly used in various biomedical technologies in recent research [55][56]. Introducing a non-invasive method for thermal destruction of biofilm on metallic implants with high-frequency (>100 kHz) alternating magnetic fields (AMF) becomes a solution for the biofilm removal especially in the treatment of prosthetic joint infection and the surgical cleaning of infected joint [57][58].…”

Formulation and characterization of Ciprofloxacin encapsulated liposomes: in vitro antimicrobial activity against multi drug resistant Salmonella typhi

“…It helps in achieving increased stability, reduced permeability leading to the maximum drug delivery with maximum encapsulation efficiency (Zhang et al, 2014). Another reason for increase encapsulation efficiency could be attributed towards using the pH gradient method for drug encapsulation as also stated in another study where ∼95% encapsulation efficiency was achieved with active loading of ciprofloxacin by a transmembrane pH gradient method (Munaweera et al, 2018).…”