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

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 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.

Natural rubber latex films with effective growth inhibition against S. aureus via surface conjugated gentamicin

“…The two-stage release profile or even three-stage in NRGC60 could be attributed to the layered deposits or penetration, and also to conjugation of the drug in the inner voids or micro-cracks present in the carboxylated film samples. 63,64…”

“…The two-stage release profile or even three-stage in NRGC60 could be attributed to the layered deposits or penetration, and also to conjugation of the drug in the inner voids or micro-cracks present in the carboxylated film samples. 63,64 Antimicrobial activity of gentamicin conjugated NRL films Compared to CNR, NRGC25, and unmodified film NRC, NRGC60 provided >60% growth inhibition against both strains. In comparison with NRC having 4.35% and 2.39% inhibition rates, NRGC60 provided 67.33% and 62.93% against S. aureus and P. aeruginosa (Figure 8) respectively.…”

“…It was also evidenced that both modifications lead to either penetration or conjugation of the drug to the voids present over the surface of the film after carboxylation so that the release gets delayed providing a multistage release profile. 63,64 Further optimization of reaction conditions could yield systems or protocols to generate a sustainable or multistage drug release system having long-term prospects. This could also provide the pathways to produce surfaces with considerable antibacterial efficacy having increased conjugation density and with the right orientation of the active molecule.…”

“…Such systems could also be considered as the right candidate for long-term (above 2 weeks) catheter applications. 63,64…”

Effect of Quorum Sensing Molecule Farnesol on Mixed Biofilms of Candida albicans and Staphylococcus aureus

“…Currently, several systemic and local therapeutic schemes, such as lock solutions, are available for the treatment of infections caused by biofilms [ 13 , 14 ]. Many investigators focus on the development of new antibiofilm and biocompatible materials with incorporated antimicrobial agents, peptides or nanomaterials [ 15 , 16 , 17 , 18 ]. Nowadays, there is a strong trend towards the development of hybrid systems of known antimicrobial compounds with more than one mode of action [ 19 ].…”