Discovery Microbiology, Aptuit S.R.L., an Evotec Company, via A. Fleming 4, 37135, Verona, Italy.
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Sci Rep. 2022 Jul 19;12(1):12329. doi: 10.1038/s41598-022-16107-4.
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.
生物材料相关性感染是一个主要的医疗保健挑战，因为它们导致重病患者的疾病负担很高。在这项研究中，我们开发了载药抗菌导管以预防导管相关性感染。尼氯硝唑（NIC）最初是一种抗寄生虫药物，通过溶剂浇铸被掺入热塑性聚氨酯（TPU）的聚合物基质中，并使用热熔挤出技术制造导管。研究了载有 NIC 的 TPU 聚合物的机械和物理化学性质。NIC 从导管中以持续的方式释放，并表现出对金黄色葡萄球菌和表皮葡萄球菌的体外抗菌活性。此外，尼氯硝唑载药导管的抗菌功效在使用耐甲氧西林敏感和耐甲氧西林金黄色葡萄球菌的体内生物材料相关性感染模型中得到了验证。从所制备的导管中释放的 NIC 减少了导管和周围组织的细菌定植。总之，尼氯硝唑释放的热熔挤出导管通过在生物材料相关性感染小鼠模型中预防植入物定植和减少耐甲氧西林敏感和耐甲氧西林金黄色葡萄球菌对导管周围组织的细菌定植，具有良好的临床前开发前景。
