Author(s)

Marilyn Porras-Gómez¹, José Vega-Baudrit¹, Fernando García², Santiago Núñez-Corrales¹, Sergio Madrigal-Carballo³

¹National Nanotechnology Laboratory (LANOTEC), National Center for Advanced Technology Studies (CeNAT), San José, Costa Rica.
²Centro de Investigaciones en Enfermedades Tropicales (CIET), Facultad de Microbiología, Universidad de Costa Rica, San Pedro, Costa Rica.
³National Center for Biotechnological Innovations (CENIBiot), National Center for Advanced Technology Studies (CeNAT), San José, Costa Rica.

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 bla_IMP-18 and bla_VIM-2 metallo-β-lactamases genes.

Chitosan, EDTA, Nanoparticles, Drug-Resistant, Imipenem

Porras-Gómez, M. , Vega-Baudrit, J. , García, F. , Núñez-Corrales, S. and Madrigal-Carballo, S. (2018) Evaluation of the Synergistic Effect of EDTA-Functionalized Chitosan Nanoparticles on Imipenem Delivery in Pseudomonas aeruginosa Carbapenem-Resistant Strain AG1. Journal of Biomaterials and Nanobiotechnology, 9, 64-78. doi: 10.4236/jbnb.2018.91006.