Innovative strategies with iron oxide nanoparticles to eradicate bacterial biofilms on implantable biomaterials

ARRIETA GAMARRA, D; CAJIAO CHECCHIN VC; GONZALEZ, A; PASQUEVICH GA; FAGALI NS

Mar del Plata

Congreso; XII Latin-American Congress of Artificial Organs and Biomaterials (12 COLAOB 2023); 2023

COLAOB

Introduction and objective: Multi-drug resistant bacteria have turned bacterial infections into a great threat to public health and the economy, which is why it is necessary to develop new methods for their eradication. The objective of this work is to develop superparamagnetic iron oxide nanoparticles (SPIONs), with an environmentally friendly synthesis method [1], to eradicate bacterial biofilms on implantable materials. The eradication of biofilms can be carried out by magnetic force, complemented by the antimicrobial effect of phytocompound capping or in association with conventional antibiotics. The SPIONs must have low cytotoxicity,antimicrobial action, adequate magnetic response, feasibility of resuspension, and stability.Methodology: Nanoparticles (NP) were synthesised by electrodeposition from Fe(II) and Fe(III) salts and coated using tannic acid (TA) at different pHs (alkaline, neutral and acid) in aqueous medium. The characterization of the SPIONs obtained was carried out using vibrating sample magnetometer (VSM), Mossbauer effect spectroscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), Fourier Transform Infrared Spectroscopy (FTIR) and thermogravimetric analysis (TGA). SPION cytotoxicity analysis was performed using the dose-responsecurve by methyl tetrazolium (MTT) reduction assay with MC3T3E.1 pre-osteoblastic cells. Preliminary bacteriological assays with Staphylococcus aureus were also performed.Results and discussion: The characterization of the SPIONs by Mossbauer and XRD confirms the obtaining of magnetite/maghemite NPs, with presence of metallic Fe. The VSM measurements show a superparamagnetic behaviour and a saturation magnetization of ~120 emu/g. This last is associated with the metallic Fe.The TA coating was confirmed by FTIR (SPIONs@TA). The alkaline TA-coating allowed better dispersibility in water and stability of the suspensions compared to NPs with neutral and acidic coatings. DLS measurements of SPIONs@TA at alkaline pH distinguish two populations, ~30 and 250 nm. SPIONs@TA at alkaline pH presented low levels of cytotoxicity (viability >80%) for suspensions up to 100 µg NPs/mL (6.9 ug Fe/ml).The TGA analysis of the NPs without capping is compatible with the magnetite NPs, showing an increase in mass from 400 °C that is explained by the oxidation of metallic Fe, possibly located in the core of the SPIONs. The TGA results for SPIONs@TA at alkaline pH confirm a higher anchoring efficiency than in the case of SPIONs@TA at other pHs. The antimicrobial effect of SPIONs@TA was assayed against S. aureus and preliminary results suggested that other strategies, such as magnetic force or combination with antibiotics, should be applied.Conclusions: SPIONs were obtained through eco-compatible technique as electrodeposit, with capping of the natural compound TA that gave them stability and low cytotoxicity. The presence of metallic Fe is possibly due to the formation of nuclei of this material covered by magnetite. TA coating at alkaline pH provides adequate physicochemical properties to SPIONs, which allows further microbiological and cytotoxicity studies.