Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria.
Research Laboratory for Implant Associated Infections (BIOFILM LAB), Experimental Orthopaedics, University Hospital for Orthopaedics and Traumatology, Medical University Innsbruck, Innsbruck, Austria.
Int J Nanomedicine. 2024 Sep 18;19:9707-9725. doi: 10.2147/IJN.S473241. eCollection 2024.
The eradication of bacterial biofilms poses an enormous challenge owing to the inherently low antibiotic susceptibility of the resident microbiota. The complexation of antibiotics with polyphosphate can substantially improve antimicrobial performance.
Nanoparticular complexes of the model drug colistin and polyphosphate (CP-NPs) were developed and characterized in terms of their particle size and morphology, polydispersity index (PDI), zeta potential, and cytotoxicity. Enzyme-triggered monophosphate and colistin release from the CP-NPs was evaluated in the presence of alkaline phosphatase (AP). Subsequently, antimicrobial efficacy was assessed by inhibition experiments on planktonic cultures, as well as time-kill assays on biofilms formed by the model organism .
The CP-NPs exhibited a spherical morphology with particle sizes <200 nm, PDI <0.25, and negative zeta potential. They showed reduced cytotoxicity toward two human cell lines and significantly decreased hemotoxicity compared with native colistin. Release experiments with AP verified the enzymatic cleavage of polyphosphate and subsequent release of monophosphate and colistin from CP-NPs. Although CP-NPs were ineffective against planktonic cultures, they showed major activity against bacterial biofilms, outperforming native colistin treatment. Strongly elevated AP levels in the biofilm state were identified as a potential key factor for the observed findings.
Accordingly, polyphosphate-based nanocomplexes represent a promising tool to tackle bacterial biofilm.
由于驻留菌群固有抗生素敏感性低，因此消除细菌生物膜是一个巨大的挑战。抗生素与多磷酸盐的络合可以显著提高抗菌性能。
开发了模型药物多粘菌素和多磷酸盐的纳米颗粒复合物（CP-NPs），并从粒径和形态、多分散指数（PDI）、zeta 电位和细胞毒性方面进行了表征。在碱性磷酸酶（AP）存在下，评估了 CP-NPs 中单磷酸盐和多粘菌素的酶触发释放。随后，通过浮游培养物的抑制实验和模型生物生物膜的时杀灭实验评估了抗菌功效。
CP-NPs 呈球形，粒径<200nm，PDI<0.25，zeta 电位为负。与天然多粘菌素相比，它们对两种人类细胞系的细胞毒性降低，血液毒性显著降低。AP 的释放实验证实了多磷酸盐的酶切以及 CP-NPs 中单磷酸盐和多粘菌素的释放。尽管 CP-NPs 对浮游培养物无效，但对细菌生物膜具有主要活性，优于天然多粘菌素处理。在生物膜状态下，AP 水平的升高被认为是观察到的结果的一个潜在关键因素。
因此，基于多磷酸盐的纳米复合物是一种有前途的解决细菌生物膜的工具。
