Positively charged biopolymeric nanoparticles for the inhibition of Pseudomonas aeruginosa biofilms

Currently, many microbial infections have the potential to become lethal owing to the development of antimicrobial resistance by means of different mechanisms and mainly on the basis of the fact that many drugs are unable to reach therapeutic levels in the target sites. This requires the use of high doses and frequent administrations, causing adverse side effects or in some cases toxicity. The use of nanoparticle systems could help overcome such problems and increase drug efficacy. In the present study, we developed a new drug delivery system based on the use of biopolymeric nanovectors loaded with tobramycin (Tb), which is the standard antibiotic for the treatment of Cystic Fibrosis-associated P. aeruginosa lung infections. Tb-loaded biopolymeric nanoparticles composed by dextran sulfate (DS) and chitosan (CS) were prepared by ionotropic gelation. We optimized drug entrapment in DS/CS nanoparticles, obtaining particles of 170 nm and with a drug loading of 400 µg Tb/mg of nanoparticles. In accord with in vitro release experiments, such preparations were able to release approximately 25 % of their cargo in 60 h. In vitro, the antimicrobial efficacy of the drug delivery system on P. aeruginosa biofilm was tested and compared to the effects of free drug revealing that this formulation can reduce the viability of P. aeruginosa biofilms for 48 h with a single-dose administration.