A Niclosamide-releasing hot-melt extruded catheter prevents Staphylococcus aureus experimental biomaterial-associated infection

Vazquez-Rodriguez, J. A.; Shaqour, B.; Guarch-Perez, C.; Choinska, E.; Riool, M.; Verleije, B.; Beyers, K.; Costantini, V. J. A.; Swieszkowski, W.; Zaat, S. A. J.; Cos, P.; Felici, A.; Ferrari, L.

doi:10.1101/2022.01.10.475592

bioRxiv · 10.1101/2022.01.10.475592

A Niclosamide-releasing hot-melt extruded catheter prevents Staphylococcus aureus experimental biomaterial-associated infection

Vazquez-Rodriguez, J. A.·Shaqour, B.·Guarch-Perez, C.·Choinska, E.·Riool, M.·Verleije, B.·Beyers, K.·Costantini, V. J. A.·Swieszkowski, W.·Zaat, S. A. J.·Cos, P.·Felici, A.·Ferrari, L.

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Abstract

Biomaterial-associated infections are a major healthcare challenge as they are responsible for high disease burden in critically ill patients. In this study, we have developed drug-eluting antibacterial catheters to prevent catheter-related infections. Niclosamide (NIC), originally a well-studied antiparasitic drug, was incorporated into the polymeric matrix of thermoplastic polyurethane (TPU) via solvent casting, and catheters were fabricated using hot-melt extrusion technology. The mechanical and physicochemical properties of TPU polymers loaded with NIC were studied. NIC was released in a sustained manner from the catheters and exhibited antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis in different in vitro models. Moreover, the antibacterial efficacy of NIC-loaded catheters was validated in an in vivo biomaterial-associated infection mouse model using a methicillin-susceptible and methicillin-resistant strain of S. aureus. The released NIC from the produced catheters reduced bacterial colonization of the catheter as well as of the surrounding tissue. A sustained in vivo release of NIC from the catheters for at least 14 days was observed. In summary, the NIC-releasing hot-melt extruded catheters prevented implant colonization and reduced the bacterial colonization of peri-catheter tissue by methicillin sensitive as well as resistant S. aureus in a biomaterial-associated infection mouse model and has good prospects for preclinical development.

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Vazquez-Rodriguez, J. A., Shaqour, B., Guarch-Perez, C., Choinska, E., Riool, M., Verleije, B., Beyers, K., Costantini, V. J. A., Swieszkowski, W., Zaat, S. A. J., Cos, P., Felici, A., Ferrari, L.. 2022-01-11. A Niclosamide-releasing hot-melt extruded catheter prevents Staphylococcus aureus experimental biomaterial-associated infection. https://doi.org/10.1101/2022.01.10.475592

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