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

Chun, Taewoo; Pattem, Jacob; Gillis, Richard B.; Dinu, Vlad T.; Yakubov, Gleb E.; Corfield, Anthony P.; Harding, Stephen E.

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.

• Journal Article Type: Article
• Acceptance Date: Jul 1, 2023
• Online Publication Date: Jul 13, 2023
• Publication Date: Jul 13, 2023
• Deposit Date: Jul 5, 2023
• Publicly Available Date: Jul 17, 2023
• Journal: Scientific Reports
• Electronic ISSN: 2045-2322
• Publisher: Springer Science and Business Media LLC
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Article Number: 11367
• DOI: https://doi.org/10.1038/s41598-023-38036-6
• Keywords: antibiotic; teicoplanin; mucin; ocular; aggregation; SV-AUC; DLS; AFM
• Public URL: https://nottingham-repository.worktribe.com/output/22719399
• Publisher URL: https://www.nature.com/articles/s41598-023-38036-6
• Additional Information: Received: 5 April 2023; Accepted: 1 July 2023; First Online: 13 July 2023; : The authors declare no competing interests.