Liquid Crystal Nanoparticles Enhance Tobramycin Efficacy in a Murine Model of Pseudomonas aeruginosa Biofilm Wound Infection

Abstract

Chronic Pseudomonas aeruginosa wound infections are highly prevalent and often untreatable due to biofilm formation, resulting in high antimicrobial tolerance. Standard antibiotic therapy for P. aeruginosa infections involves tobramycin, yet it is highly ineffective as monotherapy as tobramycin cannot penetrate the biofilm to elicit its antimicrobial effect. Lipid liquid crystal nanoparticles (LCNPs) have previously been shown to increase the antimicrobial efficacy and penetration of tobramycin against P. aeruginosa biofilms in vitro and ex vivo. Here, for the first time, we have developed a chronic P. aeruginosa biofilm infection in full-thickness wounds in mice to examine the potential of LCNPs to improve the effect of tobramycin, preclinically. After three doses, administered once a day, tobramycin-LCNPs significantly reduced the P. aeruginosa bacterial load in murine wounds 1000-fold more than unformulated tobramycin, which in turn showed no significant difference to the saline control treatment. Consistent with the improved P. aeruginosa eradication, the tobramycin-LCNPs promoted wound healing. In comparison to previous in vitro and ex vivo data, we show a strong in vitro−in vivo correlation between P. aeruginosa biofilm infection models. The enhanced activity of tobramycin-LCNPs in vivo in the preclinical murine model demonstrates the strong potential of LCNPs as a next-generation formulation approach to improve the efficacy of tobramycin against P. aeruginosa biofilm wound infections.

Novel Coumarin Derivatives Inhibit the Quorum Sensing System and Iron Homeostasis as Antibacterial Synergists against Pseudomonas aeruginosa

“…We conducted additional experiments to investigate the synergistic capability of 4t with tobramycin, another common antibiotic used for P. aeruginosa treatment. The wound area was treated with physiological saline, tobramycin (0.5 mg/mL), 42 and the tobramycin (0.0025 mg/mL)/ compound 4t (50 μM) combination, respectively. The results (Figure 8A and D) showed that the bacteria survival rate (1.78%) in the wound administered with tobramycin (0.0025 mg/mL)/compound 4t (50 μM) was significantly lower compared with that (5.77%) of the wound treated with tobramycin (0.5 mg/mL) alone after three days of continuous treatment, which showed the highly improved bactericidal potency (200-fold) of 4t with tobramycin.…”

Microenvironment‐Activated Nanozyme‐Armed Bacteriophages Efficiently Combat Bacterial Infection

“…Biofilms protect bacteria inside by providing physicochemical barriers that block the contact of antibiotics or other antibacterial substances, thus enhancing the bacterial colonization. [ 35 ] Therefore, it is important to test biofilm inhibition property of our phage@Pd to further evaluate their antibacterial functions. The classical crystal violet method was applied to quantify the biomass of biofilm.…”

Lipid Liquid Crystal Nanoparticles: Promising Photosensitizer Carriers for the Treatment of Infected Cutaneous Wounds

“…Following infection, wounds were covered with a new Tegaderm TM dressing to promote biofilm formation; the dressings were changed daily until the end of the study at day six. The progression of infection was monitored daily using an in vivo imaging system (IVIS) spectrum (PerkinElmer, Waltham, MA, USA) as previously described [ 24 ]. On day six, the mice were humanely killed, and the wound beds were collected, cut in half and used for ex vivo studies.…”