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NANO2021-Nanoteknologi og nye materiale

Nano-enabled stimuli-responsive scaffolds for targeted antimicrobials delivery to treat Staphylococcus aureus infections (TARDIS)

Awarded: NOK 4.0 mill.

Staphylococcus aureus (S. aureus) is a major causative agent of superficial and invasive skin and soft tissue infections. The occurrence of resistant S. aureus infections is a global healthcare concern reflected in poor treatment outcomes, long hospital stays and huge financial burden. TARDIS will develop innovative antimicrobial nano-enabled hydrogel scaffolds containing targeted systems with i) high bactericidal efficacy towards the pathogenic S. aureus and ii) ability to restore the beneficial microbiome balance and consequently the physiological functions of the skin. New antimicrobial marine-derived lipids and peptides will be employed for production of novel stand-alone nanoparticles with low potential for resistance development. These nano-vehicles will be incorporated into stimuli-responsive hydrogel-based 3D networks, for “on demand” delivery of the antimicrobial natural actives to the site of infection, avoiding toxic effects on human cells and beneficial skin microbiome. SINTEF Ocean extracted lipids and peptides from different marine raw materials e.g.: lipids from different fish rest raw materials (salmon, herring), fractionated fish oil into oils with different fatty acid composition, peptides from different fish rest raw materials, jelly fish (Aurelia aurita, Periphylla periphylla), gammarids. In collaboration with UPC (Spanish partners and project coordinator) several antimicrobial/ bioactivity evaluation rounds were performed. Fractions from Periphylla Periphylla showed the best antimicrobial properties. Fatty acids fractions containing higher quantities of ethyl ester (EPA) and docosahexaenoic acid (DHA) showed antimicrobial properties, but more investigations are needed and planned in the project regarding to understand fatty acid influence for antimicrobial effect. Since first theory was that fatty acids EPA and DHA has antimicrobial effect, SINTEF Ocean have grown different microalgae with a potential to produce high amounts of EPA or DHA. N. oceanica produced the highest amount of lipids, while the highest amount of polyunsaturated fatty acids was produced by C. vulgaris. The optimal conditions (i.e., algae type/harvest stage) for producing the higher values of EPA and DHA were defined. SINTEF is planning to continue growth condition optimisation and to improve the extraction efficacy.

Staphylococcus aureus (S. aureus) is a major causative agent of superficial and invasive skin and soft tissue infections. The occurrence of resistant S. aureus infections is a global healthcare concern reflected in poor treatment outcomes, long hospital stays and huge financial burden. During the infection establishment, S. aureus cell-to-cell communication process, called quorum sensing (QS), regulates the virulence factors production and formation of antibiotic resistant biofilms via the secretion of highly specific autoinducing signal molecules (AIs). TARDIS will develop innovative antimicrobial nano-enabled hydrogel scaffolds containing targeted systems with i) high bactericidal efficacy towards the pathogenic S. aureus and ii) ability to restore the beneficial microbiome balance and consequently the physiological functions of the skin. New antimicrobial marine-derived lipids and peptides will be employed for production of novel stand-alone nanoparticles with low potential for resistance development. These nano-vehicles will be incorporated into stimuli-responsive hydrogel-based 3D networks, for “on demand” delivery of the antimicrobial natural actives to the site of infection, avoiding toxic effects on human cells and beneficial skin microbiome. Taking advantage of the natural cell-cell communication principles, AIs and QS inhibitors (QSI) specifically interacting with S. aureus will be incorporated onto the surface of the developed nano-bactericides for targeted killing of the pathogen, reducing the side effects on human cells and skin microbiome. The antimicrobial efficacy and specificity of the nano-enabled hydrogels will be validated in vitro and in vivo. The treatment potential and effect of the skin microbiome balance will be further assessed by metagenome analysis, and the nano-safety of the developed antibacterials will be evaluated in accordance with OECD test guidelines.

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NANO2021-Nanoteknologi og nye materiale