TITLE:
Evaluation of the Synergistic Effect of EDTA-Functionalized Chitosan Nanoparticles on Imipenem Delivery in Pseudomonas aeruginosa Carbapenem-Resistant Strain AG1
AUTHORS:
Marilyn Porras-Gómez, José Vega-Baudrit, Fernando García, Santiago Núñez-Corrales, Sergio Madrigal-Carballo
KEYWORDS:
Chitosan, EDTA, Nanoparticles, Drug-Resistant, Imipenem
JOURNAL NAME:
Journal of Biomaterials and Nanobiotechnology,
Vol.9 No.1,
January
11,
2018
ABSTRACT: Metallo-β-lactamases
are bacterial zinc-dependent enzymes involved in the hydrolysis of β-lactamic antibiotics representing the
main cause of bacterial resistance to carbapenems, drugs of last resort for
treating infections caused by multiresistant bacteria. We elaborated the
hypothesis that it is possible to inhibit the enzymatic activity of metallo-β-lactamases by lowering the
availability of zinc in the extracellular medium using metal chelating agents
such as EDTA carried on nanoparticles. Chitosan, as linear cationic
polysaccharide is frequently used in biomedical and pharmaceutical
applications, has been studied as a biocompatible encapsulating agent in drug
delivery systems and is an ideal transport agent for bioactive molecular
complexes in antibiotic applications due to
its ability to associate with negatively charged substances. We developed
novel nanoparticles using chitosan as a transport matrix for β-lactamic antibiotics. Nanoparticles
were synthesized according to the ion gelation method using tripolyphosphate as
crosslinking agent. Nanoparticles were functionalized by the adsorption of
EDTA, which acts as complexifying agent for Zn2+ ions causing
inhibition of metallo-β-lactamases
activity. We evaluate the antimicrobial effects of EDTA-functionalized
nanoparticles with an imipenem cargo on the
clinical isolate P. aeruginosa AG1, a
carbapenem-resistant high-risk clone ST-111 carrying both blaIMP-18 and blaVIM-2 metallo-β-lactamases genes.