TY - JOUR
T1 - A Niclosamide-releasing hot-melt extruded catheter prevents Staphylococcus aureus experimental biomaterial-associated infection
AU - Vazquez-Rodriguez, Jesus Augusto
AU - Shaqour, Bahaa
AU - Guarch-Pérez, Clara
AU - Choińska, Emilia
AU - Riool, Martijn
AU - Verleije, Bart
AU - Beyers, Koen
AU - Costantini, Vivian J. A.
AU - Święszkowski, Wojciech
AU - Zaat, Sebastian A. J.
AU - Cos, Paul
AU - Felici, Antonio
AU - Ferrari, Livia
N1 - Funding Information: This research was funded by the research project PRINT-AID, the EU Framework Programme for Research and Innovation within Horizon 2020—Marie Skłodowska-Curie Innovative Training Networks under grant agreement No. 722467. Funding Information: The authors would like to thank Prof. Christophe Vande Velde from the Intelligence in Processes, Advanced Catalysts and Solvents (iPRACS) research group, Antwerp University for allowing researchers to use the thermogravimetric analysis machine in his lab. In addition, Ana Criado and Rosella Defazio for their technical assistance in the histological experimentation (Evotec, Verona, Italy); Chiara Pignaffo and Stefano Fontana (Evotec, Verona Italy) for their contribution in the in-vivo release experiments. Similarly, Jhon Quintana and Giulio Giommarelli for their assistance with the in vivo experimentation. Additionally, Mr. Jean-Pierre Smet from the Material Science department for allowing researchers to use the tensile machine in his lab. We would also like to thank Edwin Scholl and Dr. Nicole van der Wel (Electron Microscopy Center Amsterdam (EMCA), Amsterdam UMC) for their technical assistance in the collection of the SEM images. We would also like to thank Dr. Bartłomiej Wysocki and Agnieszka Chmielewska for producing the coaxial nozzle that were used to extrude the catheters. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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 an 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 in vitro antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis. Moreover, the antibacterial efficacy of NIC-loaded catheters was validated in an in vivo biomaterial-associated infection 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. 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.
AB - 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 an 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 in vitro antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis. Moreover, the antibacterial efficacy of NIC-loaded catheters was validated in an in vivo biomaterial-associated infection 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. 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.
UR - http://www.scopus.com/inward/record.url?scp=85134410711&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41598-022-16107-4
DO - https://doi.org/10.1038/s41598-022-16107-4
M3 - Article
C2 - 35854044
SN - 2045-2322
VL - 12
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 12329
ER -