Attenuation of Pseudomonas aeruginosa virulence factors and biofilms by co-encapsulation of bismuth-ethanedithiol with tobramycin in liposomes.
OBJECTIVE
This study examined the activities of tobramycin and bismuth against quorum sensing, virulence factors and biofilms of Pseudomonas aeruginosa by co-encapsulating the agents in liposomes in order to achieve greater delivery of the agents.


METHODS
The inhibitory effects of the agents, in either their conventional (free) or vesicle-entrapped (liposomal) formulations, were assessed by measuring the changes in the quorum-sensing signal molecule N-acyl homoserine lactone, pyoverdine, pyocyanin, elastase, protease, chitinase, bacterial attachment and biofilms in vitro.


RESULTS
The effectiveness of tobramycin and bismuth was superior when they were co-administered as a liposomal formulation as measured by their ability to attenuate the production of N-acyl homoserine lactone, elastase (P < 0.01), protease (P < 0.05) and chitinase (P < 0.01). In the presence of non-lethal concentrations of free and liposomal tobramycin and bismuth, bacterial attachment was attenuated. Biofilm formation was also attenuated with free tobramycin and bismuth, yet, in the presence of liposomal tobramycin and bismuth, biofilm complexes could form but contained mostly dead bacteria. When established biofilms were treated with higher concentrations, free tobramycin and bismuth killed and detached bacteria, while the liposomal tobramycin and bismuth penetrated and killed bacteria in the cores of the biofilms.


CONCLUSIONS
These data suggest that treatment of P. aeruginosa with tobramycin and bismuth, as measured by the changes in quorum sensing, virulence factors and biofilms, is most effective when delivered as a liposomal formulation at a lower concentration compared with the free formulation.
The Novel Drug & Vaccine Delivery Systems Facility, Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, P3E 2C6, Canada.
Misagh
M
Alipour
Zacharias E
ZE
Suntres
Robert M
RM
Lafrenie
Abdelwahab
A
Omri
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors; D018441:Biofilms / Q000187:drug effects*; D006801:Humans; D008081:Liposomes / Q000493:pharmacokinetics* / Q000494:pharmacology; D008623:Mercaptoethanol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D053038:Quorum Sensing / Q000187:drug effects; D014031:Tobramycin / Q000493:pharmacokinetics / Q000494:pharmacology*; D037521:Virulence Factors / Q000037:antagonists & inhibitors*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008081:Liposomes; D037521:Virulence Factors; D008623:Mercaptoethanol; C031854:1,2-ethanedithiol; D014031:Tobramycin