Metal and metal oxide nanoparticles (NPs) appeared as promising antimicrobial candidates to face the development of antibiotic resistance. Although reported as intrinsically toxic towards mammal cells, their combination with biomolecules have shown reduced toxicity, while maintaining their functionality. Herein, hyaluronic acid (HA) derivatives with molecular weight (Mw) of 40, 200 and 600 kDa have been used as reducing and capping agents to synthesise non-toxic antimicrobial hybrid silver nanoparticles (NPs). Adipic acid dihydrazide moieties grafted on the polysaccharide chains of HA (HA-ADH) enhanced the interaction between the ions and the polymer, favouring the silver reduction into NPs. TEM analysis demonstrated that the Mw of HA played a crucial role in the morphology, size and polydispersity of the NPs. Higher Mw produced smaller and more uniform HA-capped silver NPs. The antibacterial analysis further revealed that HA-ADH-Ag NPs carried out with low Mw exhibited significantly lower effect than the other two formulations. HA-ADH-Ag NPs synthesized with 40 kDa polymer reduced ~1 log the concentration of Gram-negative Escherichia coli, while 200 and 600 kDa HA-ADH capped NPs showed ~6 logs of bacterial reduction. In the case of Gram-positive Staphylococcus aureus, the NP’s antimicrobial activity achieved ~2, 3 and 6 logs reduction respectively. Langmuir isotherms were used to study of biopolymer-metal hybrid NPs interaction with a model bacterial membrane, confirming the greater interaction between bacteria and higher Mw polymers and the role of the HA modification in the antibacterial mechanisms of the NPs. Finally, the nanocomposites did not produce toxicity towards human skin fibroblast and keratinocytes cell lines in in-vitro conditions, showing more than 90 % of viability after 24h incubation with the NPs.

Biopolymer molecular weight effect on hyaluronic acid-assisted silver nanoparticles synthesis and antimicrobial performance

ACS Spring 2022

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