Liposome-Encapsulated Tobramycin and IDR-1018 Peptide Mediated Biofilm Disruption and Enhanced Antimicrobial Activity against Pseudomonas aeruginosa

Abstract

The inadequate eradication of pulmonary infections and chronic inflammation are significant complications in cystic fibrosis (CF) patients, who usually suffer from persistent and frequent lung infections caused by several pathogens, particularly Pseudomonas aeruginosa (P. aeruginosa). The ability of pathogenic microbes to protect themselves from biofilms leads to the development of an innate immune response and antibiotic resistance. In the present work, a reference bacterial strain of P. aeruginosa (PA01) and a multidrug-resistant isolate (MDR 7067) were used to explore the microbial susceptibility to three antibiotics (ceftazidime, imipenem, and tobramycin) and an anti-biofilm peptide (IDR-1018 peptide) using the minimum inhibition concentration (MIC). The most effective antibiotic was then encapsulated into liposomal nanoparticles and the IDR-1018 peptide with antibacterial activity, and the ability to disrupt the produced biofilm against PA01 and MDR 7067 was assessed. The MIC evaluation of the tobramycin antibacterial activity showed an insignificant effect on the liposomes loaded with tobramycin and liposomes encapsulating tobramycin and IDR-1018 against both P. aeruginosa strains to free tobramycin. Nevertheless, the biofilm formation was significantly reduced (p < 0.05) at concentrations of ≥4 μg/mL and ≤32 μg/mL for PA01 and ≤32 μg/mL for MDR 7067 when loading tobramycin into liposomes, with or without the anti-biofilm peptide compared to the free antibiotic, empty liposomes, and IDR-1018-loaded liposomes. A tobramycin concentration of ≤256 µg/mL was safe when exposed to a lung carcinoma cell line upon its encapsulation into the liposomal formulation. Tobramycin-loaded liposomes could be a potential candidate for treating lung-infected animal models owing to the high therapeutic efficacy and safety profile of this system compared to the free administration of the antibiotic.