替考拉宁-A2 与牛颌下黏蛋白相互作用的流体动力学和纳米成像研究——以模型眼黏液为例。

Comparative hydrodynamic and nanoscale imaging study on the interactions of teicoplanin-A2 and bovine submaxillary mucin as a model ocular mucin.

机构信息

National Centre for Macromolecular Hydrodynamics, University of Nottingham, Sutton Bonington, LE12 5RD, UK.

Soft Matter Biomaterials and Biointerfaces, School of Biosciences, University of Nottingham, Sutton Bonington, LE12 5RD, UK.

出版信息

Sci Rep. 2023 Jul 13;13(1):11367. doi: 10.1038/s41598-023-38036-6.

DOI:10.1038/s41598-023-38036-6

PMID:37443326

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10344913/

Abstract

Glycopeptide antibiotics are regularly used in ophthalmology to treat infections of Gram-positive bacteria. Aggregative interactions of antibiotics with mucins however can lead to long exposure and increases the risk of resistant species. This study focuses on the evaluation of potential interactions of the last line of defence glycopeptide antibiotic teicoplanin with an ocular mucin model using precision matrix free hydrodynamic and microscopic techniques: sedimentation velocity in the analytical ultracentrifuge (SV-AUC), dynamic light scattering (DLS) and atomic force microscopy (AFM). For the mixtures of teicoplanin at higher doses (1.25 mg/mL and 12.5 mg/mL), it was shown to interact and aggregate with bovine submaxillary mucin (BSM) in the distributions of both sedimentation coefficients by SV-AUC and hydrodynamic radii by DLS. The presence of aggregates was confirmed by AFM for higher concentrations. We suggest that teicoplanin eye drop formulations should be delivered at concentrations of < 1.25 mg/mL to avoid potentially harmful aggregations.

摘要

糖肽类抗生素常用于治疗革兰氏阳性菌感染的眼科疾病。然而，抗生素与粘蛋白的聚集相互作用会导致长时间暴露，并增加耐药物种的风险。本研究使用无精确矩阵的流体动力学和显微镜技术，重点评估了最后一线防御性糖肽类抗生素替考拉宁与眼部粘蛋白模型之间的潜在相互作用：分析超速离心中的沉降速度（SV-AUC）、动态光散射（DLS）和原子力显微镜（AFM）。对于较高剂量（1.25mg/mL 和 12.5mg/mL）的替考拉宁混合物，通过 SV-AUC 测量的沉降系数分布和 DLS 测量的水动力半径分布表明，替考拉宁与牛颌下粘蛋白（BSM）相互作用并聚集。较高浓度时，通过 AFM 证实了聚集物的存在。我们建议替考拉宁滴眼剂的浓度应低于 1.25mg/mL，以避免潜在的有害聚集。