Abstract
Cystic fibrosis (CF) is a genetic disorder in which frequent pulmonary infections develop secondarily. One of the major pulmonary pathogens colonizing the respiratory tract of CF patients and causing chronic airway infections is Pseudomonas aeruginosa. Although tobramycin was initially effective against P. aeruginosa, tobramycin-resistant strains have emerged. Among the strategies for overcoming resistance to tobramycin and other antibiotics is encapsulation of the drugs in nanoparticles. In this study, we explored the antimicrobial activity of nanoencapsulated tobramycin, both in solid lipid nanoparticles (SLN) and in nanostructured lipid carriers (NLC), against clinical isolates of P. aeruginosa obtained from CF patients. We also investigated the efficacy of these formulations in biofilm eradication. In both experiments, the activities of SLN and NLC were compared with that of free tobramycin. The susceptibility of planktonic bacteria was determined using the broth microdilution method and by plotting bacterial growth. The minimal biofilm eradication concentration (MBEC) was determined to assess the efficacy of the different tobramycin formulations against biofilms. The activity of tobramycin-loaded SLN was less than that of either tobramycin-loaded NLC or free tobramycin. The minimum inhibitory concentration (MIC) and MBEC of nanoencapsulated tobramycin were slightly lower (1–2 logs) than the corresponding values of the free drug when determined in tobramycin-susceptible isolates. However, in tobramycin-resistant strains, the MIC and MBEC did not differ between either encapsulated form and free tobramycin. Our results demonstrate the efficacy of nanoencapsulated formulations in killing susceptible P. aeruginosa from CF and from other patients.
Highlights
Cystic fibrosis (CF) is the most common genetic disorder in the Caucasian population and it is characterized by a high morbidity and mortality
While tobramycin is less nephrotoxic than gentamicin and other aminoglycosides and has been successfully used against P. aeruginosa [10], planktonic bacteria are much more sensitive than bacteria in biofilms, the growth form occurring in the lower respiratory tract of CF patients
Based on these findings and our own results demonstrating the antimicrobial activity of colistin loaded into lipid nanoparticles [20,21], in this work we explored the activity of nanoencapsulated tobramycin versus that of the free drug against P. aeruginosa clinical isolates obtained from CF patients
Summary
Cystic fibrosis (CF) is the most common genetic disorder in the Caucasian population and it is characterized by a high morbidity and mortality. It has been shown that iron regulation clearly affects susceptibility, and gene expression differences Nanoformulations such as lipid nanoparticles could improve the delivery of tobramycin and enhance its activity. Previous studies testing the effectiveness of aminoglycosides against clinical isolates of P. aeruginosa reported better results with compounds loaded in nanoformulations than with the free drug [17,18,19] Based on these findings and our own results demonstrating the antimicrobial activity of colistin loaded into lipid nanoparticles [20,21], in this work we explored the activity of nanoencapsulated (both SLN and NLC) tobramycin versus that of the free drug against P. aeruginosa clinical isolates obtained from CF patients. Microorganisms 2017, 5, 35 nanoparticles spread homogenously through the lung and there is no migration of lipid nanoparticles to other organs, such as liver, spleen, or kidneys [21]
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