Gambrill Benjamin, Pertusati Fabrizio, Shergill Iqbal, Hughes Stephen, Prokopovich Polina
Cardiff University School of Pharmacy and Pharmaceutical Sciences, Redwood Building King Edward VII Ave Cardiff CF10 3NB UK
Department of Urology, Wrexham Maelor Hospital Croesnewydd Rd Wrexham LL13 7TD UK.
Mater Adv. 2024 Dec 28;6(3):1020-1030. doi: 10.1039/d4ma01045k. eCollection 2025 Feb 3.
Urinary catheters are commonly used in medical practice to drain and monitor urine of patients. However, urinary catheterisation is associated with the risk of developing catheter-associated urinary tract infections (CAUTIs), which can result in life-threatening sepsis that requires antibiotics for treatment. Using the layer-by-layer (LbL) technique, we assembled a multilayer catheter comprising nine quadruple layers (9QL) of alginate, chlorhexidine (CHX), alginate and poly(β-amino ester) (PBAE) built upon an amino-functionalised silicone. The prepared catheter materials were tested for pre-packaged storage conditions and sterilisation techniques. The daily release of CHX was measured at pH 7.4 and pH 5 and simulated urine at 37 °C, which was used to determine the antimicrobial affect. CHX release was detected for a minimum of 14 days in PBS (pH 7.4), pH 5 release media, and simulated urine for the samples tested against storage conditions and sterilisation techniques. Incubation of the prepared material with bacterial cultures for 24 hours restricted bacterial growth compared to incubation with the standard material. The minimum inhibition concentration of CHX for clinically isolated urinary tract infection (UTI) bacterial strains was in the range of 19.4-77.4 µM, at which the released CHX could indirectly prevent bacterial growth for up to 14 days. Based on the daily CHX release from the samples, the hydrolysis of PBAE at pH 5 was gradual, resulting in a greater number of days of preventing bacterial growth, followed by pH 7.4 and then simulated urine. To the best of our knowledge, this is the first report on the use of PBAE in association with a urinary catheter material for the release of an antimicrobial drug.
导尿管在医疗实践中常用于引流和监测患者尿液。然而，导尿与发生导尿管相关尿路感染（CAUTIs）的风险相关，这可能导致危及生命的败血症，需要使用抗生素进行治疗。我们采用层层组装（LbL）技术，在氨基功能化硅胶上组装了一种多层导管，该导管由九层藻酸盐、洗必泰（CHX）、藻酸盐和聚（β-氨基酯）（PBAE）的四层结构（9QL）组成。对制备的导管材料进行了预包装储存条件和灭菌技术测试。在pH 7.4、pH 5以及37℃的模拟尿液条件下测量CHX的每日释放量，以确定其抗菌效果。在PBS（pH 7.4）、pH 5释放介质和模拟尿液中，针对储存条件和灭菌技术测试的样品检测到CHX释放至少持续14天。与标准材料孵育相比，将制备的材料与细菌培养物孵育24小时可抑制细菌生长。临床分离的尿路感染（UTI）细菌菌株对CHX的最低抑菌浓度在19.4 - 77.4 μM范围内，在此浓度下释放的CHX可间接防止细菌生长长达14天。根据样品中CHX的每日释放情况，PBAE在pH 5条件下的水解是渐进的，导致防止细菌生长的天数更多，其次是pH 7.4，然后是模拟尿液。据我们所知，这是关于将PBAE与导尿管材料结合用于释放抗菌药物的首次报道。
